THE  LIBRARY 

OF 

THE  UNIVERSITY 
OF  CALIFORNIA 

PRESENTED  BY 

PROF.  CHARLES  A.  KOFOID  AND 
MRS.  PRUDENCE  W.  KOFOID 


A  GUIDE 


TO   THE 


CLINICAL    EXAMINATION 


OF 


THE  BLOOD 


FOR  DIAGNOSTIC  PURPOSES 


BY 

EICHAED   C.   CABOT,   M.D. 


WITH  COLORED  PLATES  AND   ENGRAVINGS 


Ubirfc  1Rex>fsefc  Edition 


NEW   YORK 
WILLIAM  WOOD   AND  COMPANY 

1898 


COPYRIGHT,  1898, 
BY  WILLIAM  WOOD  AND  COMPANY. 


TO 

WILLIAM  SIDNEY  THAYEE,  M.D., 

ASSOCIATE    PROFESSOR    OF    MEDICINE    IN   JOHNS 
HOPKINS     UNIVERSITY, 

IN   GRATEFUL  RECOGNITION   OF   THE   STANDARD  OF  THOROUGH 
WORK  ESTABLISHED  BY  HIM. 


PREFACE  TO  THE  THIRD  EDITION. 


ABOUT  forty  pages  of  new  matter  have  been  added,  but  the 
book  is  no  larger  than  before,  as  a  corresponding  number  of 
pages  have  been  omitted  from  the  bibliography.  A  complete 
bibliography  of  the  subject  would  now  need  a  separate  volume, 
and  it  has  therefore  seemed  best  to  omit  all  but  the  most  im- 
portant references. 

The  principal  additions  to  the  book  include  an  account  of 
Professor  Oliver's  tintometer  and  haemoglobinometer  (which  are 
the  only  new  instruments  of  importance),  new  matter  in  the 
chapter  on  the  primary  anaemias,  and  on  leukaemia,  and  a  de- 
scription of  Miiller's  "blood-dust"  (the  newly  discovered  con- 
stituent of  normal  and  abnormal  blood).  Bremer's  and  Wil- 
liamson's tests  for  diabetic  blood  and  the  iodine  reaction  in  the 
blood  during  acute  suppurative  processes  are  described,  and 
blood  exminations  are  recorded  in  Malta  fever,  yellow  fever, 
epidemic  dropsy,  beri-beri,  relapsing  fever,  tetanus,  chicken- 
pox,  whooping-cough,  and  epidemic  cerebro-spinal  meningitis, 
diseases  not  included  in  previous  editions.  New  observations 
on  poisoning  by  alcohol,  opium,  corrosives,  and  ptomains,  on 
aneurisms,  on  paroxysmal  haemoglobinsemia,  and  on  cretinism 
are  recorded. 

I  have  wished  to  draw  especial  attention  to  the  tendency  to 
an  oval  or  sausage  shape  among  the  red  corpuscles  in  cases  of 
grave  anaemia  and  to  the  occurrence  of  adventitious  forms  of 
leucocytes  in  leucocytosis. 

Some  of  my  critics  have  regretted  that  there  was  so  little 
theoretical  discussion  in  the  book.  In  this  edition  I  have  for 
the  most  part  eliminated  what  little  there  was  before.  It  had 
already  become  out  of  date.  But  though  I  cannot  see  my  way 
to  change  the  general  plan  of  my  book,  there  has  been  hardly 
any  other  suggestion  of  my  critics  which  has  failed  to  help  me, 
I  am  especially  indebted  to  those  who  have  been  good  enough 


VI  PREFACE    TO   THE   THIRD   EDITION. 

to  send  me  detailed  criticisms,  and  in  almost  every  instance  I 
have  been  glad  to  make  the  changes  suggested.  For  such  help 
I  owe  thanks  above  all  to  Dr.  J,  B.  Herrick  of  Chicago,  Dr.  J. 
Ewing  of  New  York,  and  Dr.  Greene  of  the  Marine  Hospital 
Service. 

It  is  impossible  to  keep  such  a  book  as  this  up  to  date. 
While  the  sheets  of  this  edition  have  been  passing  through  the 
press,  three  important  works  upon  the  blood  have  appeared, 
viz.:  Ehrlich  and  Lazarus'  "Die  Anaemie,"  Turk's  "The 
Blood  in  Acute  Infectious  Diseases,"  and  Coles'  "The  Blood." 
I  have  greatly  profited  by  reading  these  books,  but  unfortu- 
nately have  been  unable  to  incorporate  their  observations  in 
the  present  edition. 

190  MARLBOROUGH  STREET,  BOSTON. 
July,  1898. 


PREFACE. 


IN  order  to  keep  the  size  of  this  book  within  reasonable  lim- 
its I  have  omitted  all  historical  account  of  the  steps  by  which 
our  present  knowledge  of  the  different  branches  of  the  subject 
has  been  built  up. 

Wherever  it  has  seemed  to  me  that  a  point  was  definitely 
established,  I  have  stated  the  conclusions  generally  accepted 
without  special  reference  to  the  names  of  those  who  worked 
them  out.  On  the  other  hand,  where  our  knowledge  has  seemed 
to  be  insufficient  I  have  given  some  of  the  names  and  findings 
of  those  who  are  responsible  for  the  opinions  generally  current. 

Theoretical  discussions  have  been  omitted  on  account  of  the 
strictly  clinical  plan  of  the  book. 

The  absence  of  any  account  of  the  origin  of  the  blood  cells, 
the  chemistry  of  the  blood,  coagulation,  and  many  other  sub- 
jects of  great  scientific  interest  is  due  to  the  lack  of  any  con- 
siderable clinical  value  in  them  so  far  as  at  present  understood. 

The  body  of  data  referred  to  from  time  to  time  as  the  "  Mas- 
sachusetts Hospital  Blood  Counts"  consists  of  nearly  four  thou- 
sand blood  examinations,  about  three  thousand  of  which  were 
made  by  Drs.  Moffitt,  Hewes,  Joslin,  Denny,  Franklin  White, 
Capps,  and  Barney — medical  internes  of  the  hospital  since  1893. 
Permission  to  avail  myself  of  these  data  was  very  kindly  granted 
me  by  the  visiting  physicians  of  the  hospital.  To  these  I  have 
added  about  one  thousand  examinations  which  I  have  made  both 
within  the  hospital  and  outside.  The  technique  used  in  all  the 
four  thousand  examinations  was  essentially  that  described  in 
the  following  pages. 

The  accumulation  of  this  body  of  facts  and  the  great  mass  of 
foreign  hsematological  literature  (untranslated)  have  seemed  to 
me  sufficient  reasons  for  the  existence  of  this  book — the  first  of 
its  kind  in  English,  so  far  as  I  am  aware.  Further,  it  has  seemed 
to  me  a  great  pity  that  there  should  be  no  book  available  con- 


VI 11  PREFACE. 

taining  colored  illustrations  of  stained  blood  preparations  which 
bear  some  resemblance  to  their  original,  and  are  not  wholly  or 
partly  works  of  the  imagination  ("diagrammatic"). 

Funke,  of  Leipsic,  has,  I  think,  been  as  successful  in  dealing 
with  the  stained  blood  in  the  present  work  as  he  was  with  the 
fresh  blood  in  the  beautiful  illustrations  for  W.  S.  Thayer's 
monograph  on  "The  Malarial  Fevers  of  Baltimore." 

Any  one  who  writes  on  the  blood  must  be  constantly  indebted 
to  the  following  standard  text-books:  Hay  em:  "Du  Sang," 
Paris,  1889.  v.  Limbeck :  "  Grundriss  einer  klinischen  Patho- 
logie  des  Blutes,"  Jena,  1896  (second  edition).  Grawitz: 
"Klinische  Pathologie  des  Blutes,"  Berlin,  1896.  Schmaltz: 
"Pathologie  des  Blutes,"  Leipsic,  1896.  Eieder:  "Beitrage  z. 
Kentniss  der  Leucocytosis,"  Leipsic,  1892. 

I  have  usually  referred  to  them  in  the  text  as  "  Hay  em, " 
"Eieder,"  etc.,  always  meaning  one  of  the  above  works. 

The  quotations  from  Schreiber  in  the  text  refer  to  manuscript 
notes  of  his  lectures  in  1896,  kindly  loaned  to  me  by  Dr.  Mark 
W.  Bichardson. 

I  am  indebted  to  Dr.  F.  P.  Henry  for  permission  to  use  the 
cuts  from  his  recent  article  on  the  filaria  sanguinis  hominis. 

December,  1896. 


PREFACE  TO  THE  SECOND  EDITION. 


A  NEW  chapter  on  the  serum  reaction  in  typhoid  fever  has 
been  added,  and  the  more  obvious  mistakes  in  the  text  have 
been  corrected.  I  wish  to  express  my  thanks  to  those  who  have 
called  my  attention  to  mistakes  in  the  text,  especially  to  Dr. 
Joseph  A.  Capps,  who  has  furnished  many  valuable  sugges- 
tions. 


TABLE  OF  CONTENTS. 


BOOK  I. 
Introduction. 

PAGE 
SCOPE  AND  VALUE  OF  BLOOD  EXAMINATION,         .        .        .   .     .        .3 

PAKT  I. 

METHODS  OF  CLINICAL  EXAMINATION  OF  THE  BLOOD* 

CHAPTER  1. 

EXAMINATION  OP  THE  FRESH  BLOOD,     .       .       .        .        .       .       .5 

(a)  Puncturing,         .         . 5 

(6)  Spreading  the  Blood,          .         . 7 

(c)  Prevention  of  Cell  Death, 8 

(d)  Knowledge  to  he  Gained  from  Fresh  Blood 9 

CHAPTER  II. 

COUNTING  THE  CORPUSCLES, 11 

(a)  Sucking  Up  the  Blood, 11 

(&)  Diluting  the  Blood, 12 

(c)  Adjusting  the  Diluted  Blood  in  the  Counting  Chamber,           .  14 

(d)  Counting  the  Red  Corpuscles,    .         .         .         .         .         .         .15 

(e)  Counting  the  White  Corpuscles, 18 

(/)  Counting  both  Red  and  White  Corpuscles  with  One  Pipette,  .  19 

(g)  Durham's  Hsemocytometer,       .......  22 

CHAPTER  III. 

OLIVER'S  TINTOMETER— CENTRIFUGALIZING  THE  BLOOD— HAEMOGLOBIN 
ESTIMATION— SPECIFIC  GRAVITY— STAINED  SPECIMENS— BAC- 
TERIOLOGICAL EXAMINATION. 

1.  Oliver's  Tintometer, 26 

2.  Daland's  Haematocrit,  Its  Objects, ,29 

Use  of  the  Haematocrit, 30 

3.  Use  of  v.  Fleischl's  Haemometer, 33 

Necessary  Errors  in  Its  Use,        ...  .37 

4.  Oliver's  Haemoglobinoineter,       .  .     38 


TABLE  OF  CONTENTS. 

PAGE 

5.  Specific  Gravity  Estimation,        .         .         .        .        .        .        .40 

Hammerschlag's  Method,   .....,.„     41 

6.  Study  of  Dried  and  Stained  Specimens,       .        .        .        .        .43 

(a)  Preparation  of  Cover-Glass  Specimens,       .        .        .        .43 
(6)  Fixing  Cover-Glass  Specimens, 43 

(c)  Staining,       .         .         .         .         .         ....         .44 

(d)  Differential  Counting  (color  analysis),      .        .        .        .46 

7.  Bacteriological  Examination, 47 

8.  Other  Methods  of  Examination, 48 


PAKT  H. 

PHYSIOLOGY  or  THE  BLOOD. 

CHAPTER  IV. 

MORPHOLOGY  OP  FRESH  BLOOD, 50 

(a)  Appearances  of  Normal  Red  Corpuscles, 50 

(b)  Appearances  of  Normal  White  Corpuscles 52 

(c)  Appearances  of  Normal  Blood  Plates 53 

(d)  Appearances  of  Fibrin  Network,        .         .         .         .         .         .53 

(e)  Average  Diameter  of  Red  Cells 55 

(/)  Normal  Number  of  Red  Cells, .         .  56 

Influence  of  Menstruation,  Parturition,  Lactation,           .         .  56 
Influence  of  Vasomotor  Changes,       .         .         .        .         .         .57 

(g)  Influence  of  Nutrition  on  the  Red  Cells, 57 

Influence  of  Fatigue  on  the  Red  Cells, 58 

(h)  Normal  Number  of  White  Cells 58 

(i)  Normal  Number  of  Blood  Plates, 59 

(j)  Muller's  Blood-dust, 59 

CHAPTER  V. 

FINER  STRUCTURE  OF  THE  BLOOD,          .       .       .  .        .        .61 

1.  Finer  Structure  of  Red  Cells, 61 

2.  Finer  Structure  of  White  Cells  and  Their  Varieties, 

(a)  Lymphocytes, 62 

(6)  Transitional  Cells, 63 

(c)  Polymorphonuclear  Neutrophiles, 64 

(d)  Eosinophiles,        ......•••  65 

(e)  Basophiles, 66 

Terminology, 67 

Normal  Percentage  of  Each  Variety,          .        .        .        .67 

(/)  Myelocytes, 69 

Eosinophilic  Myelocytes, ^ 

Cornil's  "Markcellen," 71 


TABLE   OF   CONTENTS.  XI 

PAET  III 

GENERAL  PATHOLOGY  OF  THE  BLOOD. 

CHAPTER  VI. 

PAGE 

UNEQUAL  DISTRIBUTION  OF   THE  BLOOD— PLETHORA — DILUTION  AND 

CONCENTRATION  OF  THE  BLOOD, 73 

1.  Unequal  Distribution,  .         .         .         .         .         .  .73 

2.  Apparent  Polycythaemia, 73 

(a)  General  Cyanosis,         .        .        .  .        .        .        .74 

(&)  Local  Cyanosis, 74 

(c)  Feeble  Circulation, 75 

3.  Plethora— Serous  or  Cellular, 75 

4.  Concentration  of  the  Blood,          .        .        .        .        .        .         .76 

5.  Dilution  of  the  Blood, 78 

6.  The  Blood  in  High  Altitudes, 79 

7.  Phosphorus  and  CO  Poisoning, 80 

8.  Possibility  of  a  True  Plethora, 80 

CHAPTER  VII. 

ANAEMIA  AND  HYDR^EMIA, 82 

(a)  Pallor  and  Anaemia, 82 

(6)   "Tropical  Anaemia," .        .83 

(c)  Distinction  Between  Primary  and  Secondary  Anaemia,     .  84 

Secondary  Anaemia, 85 

1.  First  Stage— Loss  of  Color,  Weight,  and  Size,      .         .         .  85 

2.  Second  Stage — Poikilocytosis  and  Degeneration,          .         .  85 

(a)  Endoglobular  Changes, 86 

(6)  Crenation  and  Deformities ;  Motility,          .        .        .86 

(c)  Oval  Shape, 87 

(d)  Changes  in  Staining  Properties,          .           ...  88 

(e)  Loss  of  Haemoglobin,   ....           ...  88 

3.  Third  Stage— Deglobularization, 89 

4.  Nucleated  Red  Corpuscles, 89 

(a)  Normoblasts, .  90 

(b)  Megaloblasts, 91 

(c)  Microblasts, 92 

(d)  Atypical  Varieties, 92 

Summary, 94 

Hydraemia, 95 

CHAPTER  VIII. 

LEUCOCYTOSIS,  LYMPHOCYTOSIS,  EOSINOPHILIA,  AND  MYELOCYTES,     .    96 

Definition  of  Leucocytosis, 96 

Physiological  Leucocytosis,      .  .         ...         .        .         .98 


Xll  TABLE   OF   CONTENTS. 

PAGE 

(a)  Effects  of  Nutrition  and  Starvation, 99 

(&)    Digestion  Leucocytosis,                .                          ...  99 

Its  Diagnostic  Value,           .......  100 

(c)  Leucocytosis  of  the  New-Born, 101 

(d)  Leucocytosis  of  Pregnancy, 101 

(e)  Leucocytosis  after  Parturition, 102 

(/)  Leucocytosis  from  Exercise,  Massage,  and  Baths,      .         .  102 

(g)  Terminal  Leucocytosis, 105 

Pathological  Leucocytosis, 106 

(a)  Post-hemorrhagic  Leucocytosis,         .....  106 

(6)   Inflammatory  Leucocytosis 106 

(c)  Toxic  Leucocytosis, 109 

(d)  Leucocytosis  due  to  Therapeutic   and  Experimental  In- 

fluences,  110 

(e)  Morphology  of  the  Leucocytes  in  Leucocytosis,          .         .  112 

Absence  of  Leucocytosis, 113 

Leucopenia, .  113 

Lymphocytosis, 114 

Diagnostic  Value  of  Lymphocytosis,          ...  116 

Eosinophilia,     .........  116 

Diminution  of  Eosinophiles, 119 

Diagnostic  and  Prognostic  Value  of  Eosinophilia,  .         .  119 

Myelocytes,        . 120 

CHAPTER  IX. 

GENERAL  PATHOLOGY  OP  HAEMOGLOBIN  AND  FIBRIN,  LIP^EMIA,  MEL- 

ANAEMIA  AND  HEMORRHAGE, .123 

1<  Haemoglobin  and  the  "Color  Index," 123 

2.  Fibrin, 124 

3.  Lipaemia,       ...........  125 

4.  Melanaemia, 126 

5.  Hemorrhage, 126 

(a)  Changes  in  the  Blood  Resulting  from  Hemorrhage,  .        .  126 
(&)  Blood  Regeneration,    .         .         .         .         .         .         .         .127 

Regeneration  of  Red  Cells, 127 

Blood  Crisis, 128 

Regeneration  of  White  Cells, 128 

Importance  for  Surgery  of  Blood  Counting  after  Hemorrhage,       .  129 
Chronic  Hemorrhage 130 


TABLE   OF   CONTENTS.  Xlll 

BOOK  II. 
Special  Pathology  of  the  Blood. 

PART  I. 

DISEASES  OF  THE  BLOOD. 

CHAPTER  I. 

PAGE 

FHE  PRIMARY  ANEMIAS, 

1.  The  Blood  in  Pernicious  Anaemia, 133-151 

1.  Gross  Appearances, 

2.  Appearances  of  Fresh  Blood,           .....   133 
Red  Cells  and  Haemoglobin, 

Quantitative  Changes, 134-137 

White  Cells, 137 

Quantitative  Changes, 137 

Blood  Plates  and  Fibrin,      .......  138 

Haemoglobin, 138 

Qualitative  Changes 139 

1.  Red  Corpuscles, 139 

(a)  Increase  in  Diameter, 139 

(6)  Deformities  in  Shape, 140 

(c)  Staining  Properties, 141 

(d)  Nucleated  Red  Corpuscles,      ....    141-144 

2.  White  Corpuscles,  .  ....    144-147 
Characteristics  of  Pernicious  Anaemia,  Summary,  .         .        .   146 
Differential  Diagnosis  of  Pernicious  Anaemia,  .   147 

1.  Pernicious  Anaemia  and  Chlorosis,         .  .147 

2.  Pernicious  Anaemia  and  Malignant  Disease,  ,         .   147 

3.  Pernicious  Anaemia  and  other  Secondary  Anaemias,     .  148 

4.  Pernicious  Anaemia  and  Leukaemia,       ....   148 
Prognostic  Value  of  the  Blood  in  Pernicious  Anaemia,    .         .   149 

2    The  Blood  in  Chlorosis 152 

The  Blocd  in  Gross, 152 

1.  Red  Cells  and  Haemoglobin, 152 

(a)  Quantitative  Changes,    .         .         •        .        •        .152 
(&)  Qualitative  Changes 155 

2.  Specific  Gravity, 156 

3.  White  Cells 156 

(a)  Quantitative  Changes, 156 

(6)  Qualitative  Changes 156 

4.  Blood  Regeneration  in  Chlorosis,   .... 

5.  Chlorosis  without  Known  Blood  Changes,    .          .  157 

6.  Summary  and  Diagnostic  Value,  .         .         .          .         •    157 
3.  Other  Forms  of  Anaemia,    ......          •  158 


XIV  TABLE   OF   CONTENTS. 

CHAPTER   II. 

PAGE 

LEUKAEMIA  AND  HODGKIN'S  DISEASE,     .        .        .        .        .        .        .160 

1.  Myelocytsemia,     ......         „         .         .         .  161 

1.  Red  Cells, •       .  161 

(a)  Quantitative  Changes, 161 

(6)  Qualitative  Changes, 162 

2.  White  Cells, 163 

(A)  Quantitative  Changes,          .         .         .         .'."".         .  163 

(B)  Qualitative  Changes, .165 

(a)  Myelocytes, 165 

(6)  Polymorphonuclear  Cells 166 

(c)  Lymphocytes, 167 

(d)  Eosinophiles, .  167 

(e)  Basophiles, 168 

(f)  Polymorphous  Condition  of  the  Blood,           .         .  169 

2.  Lymphaemia, 169 

1.  Red  Cells, 170 

2.  White  cells, 170 

(a)  Quantitative  Changes, 170 

(&)  Qualitative  Changes,              171 

Summary  of  Blood  Changes  in  Leukaemia,        ....  173 

Differential  Diagnosis  of  Leukaemic  Blood,       ....  174 

(a)  From  Hodgkin's  Disease, 174 

(5)  From  Tumors  in  or  near  Spleen,  .         .         .         .        .  174 

(c)  From  Syphilitic  or  Tubercular  Adenitis,      .         .         .  175 

(d)  From  Hydronephrosis,          ......  175 

(e)  From  Leucocytosis, 175 

(/)  From  Chronic  Malaria  or  Amyloid  Diser.se,       .         .  175 

Table  of  Differential  Diagnosis  in  Leukaemia,           .         .         .  175 

Effect  of  Intel-current  Infections  in  Leukaemia,        .         .         .  176 

Hodgkin's  Disease •  .  177 

(a)  Red  Cells, 179 

(6)  White  Cells, 181 

(c)  Summary  and  Diagnostic  Value,         .  .         .     181-182 


PAET  II. 

ACUTE  INFECTIOUS  DISEASES. 

INTRODUCTION. 
EFFECTS  OF  FEVER  ON  THE  BLOOD,         .  .  188 

CHAPTER  III. 

PNEUMONIA,  TYPHOID,  AND  DIPHTHERIA, 184 

I.  Pneumonia,     . 184 

'    1.    (a)   Bacteriology  of  the  Blood.  .        .        .184 


TABLE   OF   CONTENTS.  ^V 

PAGE 

(&)    Coagulation  and  Fibrin, ^5 

(c)   Concentration  of  the  Blood,     ,  ...  185 

2.  Red  Cells, ...  185 

3.  White  Cells, 185 

(a)  Quantitative  Changes 185 

(b)  Qualitative  Changes 187 

4.  Diagnosis  and  Prognosis, 1' 

II.  Typhoid  Fever, >  1! 

1.  Bacteriology  and  the  Serum .        .  1! 

2.  Red  Cells  and  Haemoglobin, 191 

3.  White  Cells, 193 

4.  Effect  of  Complications  on  White  Cells,         .        .        .        .194 

5.  Qualitative  Changes  in  the  White  Cells,        .        .        .        .195 

6.  Summary  and  Diagnostic  Value, 196 

III.  Diphtheria, 197 

(a)  Red  Cells l! 

(&)  Haemoglobin, 1 

(c)  White  Cells, 199 

(d)  Summary .         .  201 


CHAPTER  IV. 

ACUTE  INFECTIOUS  DISEASES  (Continued). 

I.  Scarlet  Fever, 203 

(a)  Red  Cells, 203 

(6)  White  Cells, 203 

(c)   Summary  and  Diagnostic  Value 204 

II.  Measles,  Rotheln,  and  Mumps, 205 

III.  Whooping-Cough, 306 

IV.  Small-pox  (Variola), 

V.  Chicken-pox, 

VI.  Acute  Articular  Rheumatism, 

(a)  Fibrin,  Alkalinity,  Red  Cells,     .  •  307 

(6)   White  Cells  in  Acute  Forms,       .... 

(c)  White  Cells  in  Subacute  Forms, 

(d)  White  Cells  in  Chronic  and  Muscular  Forms,    . 

(e)  Summary  and  Diagnostic  Value, 

VII.  Asiatic  Cholera, 

VIII.  Erysipelas,       .... 

IX.  Tonsillitis 

X.  Grippe 

XI.  Septirsemia, 

(a)  Bacteriology  of  the  Blood, 

(b)  Red  Cells,     .         . 

(c)  White  Cells, 

(d)  Summary  and  Diagnostic  Value, 

XII.  A.  Abscess,  Iodine  Reaction  in,       .... 


XVI  TABLE   OF   CONTENTS. 

PAGE 

B.  Appendicitis,         ...  223 

(a)  Leucocytosis,         .         .         .         .         .         .         .    223-229 

(6)  Significance  of  the  Absence  of  Leucocytosis,       .         .  227 
(c)  Differential  Diagnosis, 229 

C.  Pus  Tube,  Pelvic  Abscess,  and  Pelvic  Peritonitis,       .         .  231 

Differential  Diagnosis .232 

D.  Otitis  Media, 233 

E.  Osteomyelitis, 234 

F.  Other  Abscesses,     .  .  234 

Diagnostic  Value, 235 

XIII.  Gonorrhoea, 236 

XIV.  Yellow  Fever,  . .236 

XV.  Typhus  Fever, 237 

XVI.  Malta  Fever, 238 

XVII.  Relapsing  Fever 238 

XVIII.  Glanders, .238 

XIX.  The  Bubonic  Plague,       .  .  238 

XX.  Actinoraycosis,          .........  239 

XXI.  Trichinosis,     ...  ...  239 

XXII.  Epidemic  Dropsy, 240 

XXIII.  Tetanus, 241 

XXIV.  Beri-beri,      .  .  241 

CHAPTER  V. 

DISEASES  AFFECTING  THE  SEROUS  MEMBRANES,    .....  242 

I.  Serous  Pleurisy, .242 

(a)  Summary  and  Diagnostic  Value,         .         .  .         .  244 

(6)  Purulent  Pleurisy  (Empyema) ,  .         .  .  244 

II.  Peritonitis, .245 

Diagnostic  Value,        ...  .246 

III.  Pericarditis  (with  Effusion),    ....  .247 
Diagnostic  Value,        ....                                            .248 

IV.  Meningitis,          .  .  248 
Epidemic  Cerebro-Spinal  Meningitis,                                             .  249 
Diagnostic  Value,        .......                  •  251 


PART  III. 

CHRONIC  INFECTIOUS  DISEASES. 
CHAPTER  VI. 

TUBERCULOSIS,  SYPHILIS,  AND  LEPROSY, 253 

I.  Tuberculosis, 253 

1.  Red  Cells  and  Heemoglobin,  ...  .253 

(a)  Quantitative  Changes,  ......  253 


TABLE    OF   CONTENTS.  xvii 

PAGE 

(6)  Qualitative  Changes,     .  .   254 

2.  Leucocytes,     ....  .  255 

(a)  Changes  in  Phthisis,  '  .  .   255 

(b)  Changes  in  Bone  Tuberculosis  and  Cold  Abscess,         .  259 

(c)  Changes  in  Acute  Miliary  Tuberculosis,       .         .         .   261 

(d)  Changes  in  Tubercular  Peritonitis,       ....   264 
(<?)   Changes  in  Tubercular  Meningitis,       ....  265 
(/)  Changes  in  Tubercular  Pericarditis,    ....  267 
(g)  Changes  in  Tubercular  Pleurisy,  ....  267 
(h)  Changes  in  Glandular  Tuberculosis,      ....  267 
(i)    Changes  in  Genito-Urinary  Tuberculosis,    .         .         .268 

II.  Syphilis, .  268 

1.  (a)  Changes  in  Red  Cells  and  Haemoglobin,         .        .        .269 
(b)   Justus'  Reaction, ,270 

2.  Changes  in  White  Cells 270 

Diagnostic  Value 271 

III.  Leprosy 272 


PART  IY. 

DISEASES  OF  SPECIAL  ORGANS. 

CHAPTER  VII. 

DISEASES  OF  THE  DIGESTIVE  ORGANS, 274 

I.  Diseases  of  the  Stomach, 274 

(a)  Peptic  Ulcers — Gastric  or  Duodenal,  .         .         .         .  275 

1.  Red  Cells, 275 

2.  White  Cells, 277 

(6)  Gastritis  and  Dyspepsia,       .......  278 

.(c)  Chronic  Gastritis, 279 

(d)  Hyperacidity  and  Hypersecretion, 280 

(e)  Dilated  Stomach, 280 

(/)  Corrosive  Gastritis, 281 

II.  Diseases  of  the  Intestines,  ........  281 

Influence  of  Saline  Cathartics  on  the  Blood 281 

(a)  Acute  Enteritis .282 

(b)  Chronic  Diarrhoea, 282 

(c)  Intestinal  Obstruction,          .......  284 

III.  Diseases  of  the  Liver,         ........  284 

(a)  Catarrhal  Jaundice, 284 

Qualitative  Changes  of  Red  Cells, 285 

Summary  and  Diagnostic  Value, 286 

(&)  Cirrhosis  of  the  Liver, 286 

1.  Ordinary  (Atrophic)  Cirrhosis  without  Jaundice,  .  286 
Qualitative  Changes  of  Red  Cells  and  Haemoglobin,  .  286 
White  Cells, 288 


XV111  TABLE   OF   CONTENTS. 

PAGE 
2.  Hypertrophic  Cirrhosis  with  Jaundice,          .        .         .  288 

Red  Cells  and  Haemoglobin, 288 

White  Cells, 289 

Diagnostic  Value, 289 

(e)  Hydatid  Cyst  of  the  Liver, 289 

(d)  Acute  Yellow  Atrophy  of  the  Liver,  .        .        .        .289 

(e)  Phosphorus  Poisoning, 290 

(/)  Cholaemia, 290 

(gr)  Gall-stones, 290 

(h)  Cholangitis, 291 

(i)  Abscess  of  the  Liver 292 

(j)  Cancer  of  the  Liver, 292 

(&)  Gumraa  of  the  Liver, 293 

Diseases  of  the  Heart,        . 293 

(a)  Pericarditis 293 

(6)  Endocarditis, 293 

Red  Cells, 293 

White  Cells, 294 

Diagnostic  Value, 295 

(c)  Myocarditis,          . 295 

(d)  Valvular  Heart  Disease, 296 

Red  Cells,      .  296 

White  Cells, 297 

(e)  Congenital  Heart  Disease, 298 

(/)  Aneurism 299 

Diseases  of  the  Kidneys, 299 

(a)  Acute  Nephritis, 300 

Red  Cells  and  Haemoglobin, 300 

White  Cells, 301 

(6)   Chronic  Diffuse  Parenchymatous  Nephritis,       .         .         .   302 
Red  Cells  and  Haemoglobin,         .         .         .         .         .         .302 

White  Cells, 303 

(c)  Chronic  Interstitial  Nephritis, 304 

(d)  Pyelo-nephritis 205 

(e)  Stone  in  the  Kidney, 306 

Diagnostic  Value,         ........  306 

(/)  Floating  Kidney,         ....  ...  307 

(g)  Pyonephrosis, 307 

Diseases  of  the  Lungs,       .         .  .307 

(a)  Bronchitis,   ...  ..807 

(1)  Acute  Bronchitis,  .  307 

(2)  Chronic  Bronchitis,  ...                                   .  308 

(b)  Emphysema  and  Asthma, 309 

(c)  Syphilis  of  the  Lung,   .  310 


TABLE   OF   CONTENTS.  XIX 


PAET  V. 

DISEASES  OP  THE  NERVOUS  SYSTEM,  CONSTITUTIONAL  DISEASES 
AND  HEMORRHAGIC  DISEASES. 

CHAPTER   VIII. 

PAGE 

DISEASES  OF  THE  NERVOUS  SYSTEM,       .        .        .        .       .       .        .311 

1.  Neuritis, 311 

(a)  Acute  Multiple  Neuritis,      .        .        .        .        .        .        .311 

(6)  Alcoholic  Neuritis 311 

2.  Neuralgia, 312 

3.  Diseases  of  the  Brain, 312 

(a)   Pachymeningitis 312 

(6)  Cerebral  Syphilis, 312 

(c)  Cerebral  Tumor, 312 

(d)  Cerebellar  Tumor, .312 

(e)  Cerebral  Haemorrhage, 312 

4.  Chorea  and  Tetanus, 313 

5.  Chronic  Diseases  of  the  Spinal  Cord, 313 

Tabes  Dorsalis, 313 

Syringomyelia,   .         .         .         .         .         .         .         .         .         .313 

Spastic  Paraplegia, 313 

Diffuse  Myelitis, 313 

Paralysis  Agitans, 313 

Progressive  Muscular  Atrophy, 313 

6.  General  Paralyses  of  the  Insane,    ...          ....  313 

7.  Hysteria,  Neurasthenia,  and  Hypochondriasis,    ....  314 

8.  Mental  Diseases, 315 

Constitutional  Diseases,     .        .        .        .        .        .        .        .        .        .315 

(1)  Obesity,          .        .        .        .        .        .        .        .        .        .        .315 

(2)  Diabetes, 316 

Red  Cells, 317 

White  Cells, 317 

(3)  Gout, .        .        .317 

(4)  Myxcedema, 318 

(5)  Cretinism, 319 

(6)  Graves'  Disease 320 

(7)  Addison's  Disease .320 

(8)  Osteomalacia, 321 

(9)  Rickets, 322 


CHAPTER  IX. 

BLOOD  DESTRUCTION  AND  HEMORRHAGIC  DISEASES,      ....  324 

I.  Hemorrhagic  Diseases, 324 

1.  Purpura  Haemorrhagica,          .......  324 


XX  TABLE   OF   CONTENTS. 

PAGE 

2.  Scurvy  and  Barlow's  Disease, 335 

3.  Haemophilia,     ........  325 

II.  Blood  Destruction,          ...  ...  326 

1.  Hsemoglobinsemia  in  Infectious  Diseases,      ....  326 

2.  Paroxysmal  Hagmoglobinaemia,       .         .         .  .  326 

3.  Burns,  Snake  Poison,  etc. , 327 

4.  Poisons,  Chlorate  of  Potash,  Antipyretics,  etc.,    . .       .         .327 

5.  Illuminating  Gas, 330 

6.  Tansy  Poisoning, 330 

7.  Corrosive  Poisoning,  .........  330 

8.  Opium  Poisoning,    .........  330 

9.  Ptomain  Poisoning, .  331 

10.  Acute  Alcoholism,   .         .        .         .        .        .         .        .         .331 

PAKT  YI. 

MALIGNANT  DISEASE,  BLOOD  PARASITES,  AND  INTESTINAL 
PARASITES. 

CHAPTER  X. 

MALIGNANT  DISEASES, 332 

1.  Cancer, 332 

I.  Red  Cells, 332 

(a)  Quantitative  Changes, 333 

(&)  Haemoglobin, 334 

(c)  Regeneration  of   Blood  after  Operations  on  Cancer- 
ous Growths, 335 

(d)  Qualitative  Changes  in  Red  Cells,         .        .        .        .337 

11.  White  Cells, 338 

(a)  Influence  of  Position  and  Size  of  Tumor,     .        .        .339 
(6)  Influence  of  Individual  Constitution,  .        .        .  339 

(c)  In  Cancer  of  the  Breast, 340 

(d)  In  Cancer  of  the  Stomach, 341 

(e)  Digestive  Leucocytosis  in  Gastric  Cancer,   .        .        .  343 
(/)  Effect  of  Metastases  in  Gastric  Cancer,         .        .        .   344 

(g)  In  Cancer  of  the  Gullet, 345 

(7t)  In  Cancer  of  the  Liver, 340 

(i)  In  Cancer  of  the  Intestine, 347 

(;)  In  Cancer  of  Omen  turn  and  Abdominal  Organs  Gener- 
ally,           348 

(ft)  In  Cancer  of  the  Kidney, 348 

(1)  In  Cancer  of  the  Uterus, 349 

(m)  In  Cancer  of  other  Organs, 349 

Qualitative  Changes  of  Leucocytes  in  Cancer 350 

(a)   Polymorphonuclear  Cells, 350 

(6)  Eosinophiles, .         .         .  351 


TABLE    OF    CONTENTS.  XXI 

PAGE 
(c)  Myelocytes, 351 

2.  Sarcoma, 353 

Red  Cells  and  Haemoglobin, 353 

White  Cells  in, 354 

Qualitative  Changes  of  Leucocytes  in  Sarcoma,         .         .         .  356 

(a)  Poly  morphonuclear  Cells, 356 

(b)  Eosinophiles, 356 

(c)  Myelocytes, .        .        .357 

Summary  and  Diagnostic  Value, 358 

CHAPTER  XI. 

BLOOD  PARASITES  AND  INTESTINAL  PARASITES,      .  ...  361 

1.  Examination  for  the  Plasmcdium  Malarias  and  Its  Products,     .  361 

I.  Time  of  Examination, 361 

II.  Method  of  Examination, 361 

III.  The  Malarial  Organism  Described, 362 

(a)  Recognition  of  Hyaline  Forms,     .....  362 
(6)  Pigmented  Forms, .363 

(c)  Segmentation, 366 

(d)  Flagella  and  Pigmented  Leucocytes,     ....  367 

(e)  Crescents 367 

IV.  Staining  the  Malarial  Organism 370 

V.  Other  Changes  in  the  Blood 373 

Red  Corpuscles 372 

Haemoglobin,         .         .        . 372 

White  Cells, 373 

Malarial  Haemoglobinaemia, 374 

3.  Filaria  Sanguinis  Hominis, 374 

3.  Spirochaete  of  Relapsing  Fever, 37J 

Technique  of  Examination,          .        .        .        .        ..       .  382 

4.  Distomum  Haematobium, 382 

5.  Bacteria  in  the  Blood 383 

(a)  Cover-Glass  Specimens, 383 

(5)  Cultures, 383 

Anaemia  due  to  Intestinal  Parasites,  .....  383 

CHAPTER  XII. 

THE  BLOOD  IN  INFANCY, 385 

(a)  General  Characteristics,       . 385 

(b)  The  Anaemias  of  Infancy, 387 

1.  Classification, 388 

2.  Secondary  Anaemias,       ........  388 

3.  "Anaemia  Infantum  Pseudoleukaemica,"       ....  391 

4.  Importance   of  the  Term  as  Indicating  the   Difficulty  of 

Classifying  the  Anaemias  of  Infancy 391 

5.  Pernicious  Anaemia  in  Infancy,     ......  395 

6.  Leukaemia  in  Infancy, 397 


XX11  TABLE   OF   CONTENTS. 

PAKT  YII. 

EXAMINATION  OF  THE  SEBUM. 
CHAPTER  XIII. 

PAGE 

THE  CLUMP  REACTION,      .        .  .        ••*••.  4QO 

1.  General  Description, 40Q 

2.  Technique, 4Qo 

(a)  The  Body  Fluids  Used, 402 

(6)  Use  of  the  Whole  Blood— Fluid, 402 

(c)  Use  of  the  Whole  Blood— Dried, 404 

(d)  Use  of  the  Serum — Fluid  ;  Quick  Method,          .        .        .  4Q6 

(e)  Use  of  the  Serum — Fluid  ;  Slow  Method,    ....  4Q7 

(/)  Use  of  Blister  Fluid, 408 

(g)  Relative  Advantages  of  the  Slow  and  of  the  Quick  Method,  4og 

(ft)  The  Cultures  to  be  Used, -409 

(i)  The  Use  of  Suspensions  instead  of  Cultures,        .        .        .  4u 

(j)  The  Use  of  Attenuated  Cultures, 4H 

(fc)  The  Clump  Reaction  with  Dead  Bacilli,     .        .        .        .  4u 
(Z)  Dilution  and  the  Time  Limit, -412 

3.  Sero  Diagnosis  of  Typhoid  Fever, 415 

(a)  General  Statistics,         .        .         .         •.        .        .        „        -415 

(b)  How  Early  does  the  Reaction  Appear?         ....  4i5 

(c)  How  Late  does  the  Reaction  Last?       .  '  .        .         «  416 

(d)  The  Intensity  of  the  Reaction,     ......  417 

(e)  Effects  of  Sera  of  Other  Diseases  on  Typhoid  Bacilli,        .  4ig 
(/)  Summary  of  Negative  Results, 419 

4.  Effects  of  Typhoid  Serum  on  Other  Bacilli,          ....  430 

(a)  On  the  Bacillus  Coli  Communis, 420 

(b)  On  the  Bacillus  Enteritidis  (Gartner),        ,        .        .        .  420 

(c)  On  the  Bacillus  of  Psittacosis ..421 

(d)  On  the  Klebs-Loeffler  Bacillus  and  Pus  Cocci,  .        .        .  421 

(e)  Summary  of  Clinical  Evidence, 421 

5.  Sero -Diagnosis  of  Other  Diseases,         .  421 

(a)  Cholera, 422 

(b)  Pyocyaneus  Infections,         .......  422 

(c)  Diphtheria, c  422 

(d)  Pneumococcus  Infections, 422 

(e)  Colon  Bacillus  Infections,     .        .        .        .        .        .        .423 

(/)  Malta  Fever,  .  424 

(g)  Peripneumonia  of  Cattle,  and  Hog  Cholera,       .        .        .  424 

(h)  Proteus  Infections, 424 

(i)  Oidium  Albicans,  ........  425 

(j)  Bubonic  Plague,     .....  ...  425 

(fe)  Yellow  Fever,         . 425 


TABLE   OF  CONTENTS.  XX111 

PAGE 

(1)  Relapsing  Fever, 425 

(m)  Miscellaneous  Reports  on  Scarlet  Fever,  Tetanus,  Septi- 
caemia, and  Psittacosis, 426 

6.  Sero-Prognosis, 427 

APPENDIX— Neusser's  " Perinuclear  Basophilic  Granules,"     .        .        .399 

BIBLIOGRAPHY, 429 

INDEX, 433 


BOOK    I. 


INTRODUCTION. 


SCOPE  AND  VALUE  OF  BLOOD  EXAMINATION. 

H^EMATOLOGY  is  still  so  new  a  study  that  no  confident  state- 
ment can  be  made  as  to  the  exact  limits  of  its  usefulness  in  the 
practice  of  medicine.  It  has  solved  some  problems  where  least 
was  hoped  from  it,  and  given  us  disappointingly  little  help 
where  great  expectations  had  been  aroused.  We  might  have  ex- 
pected from  it  some  light  on  the  nature  of  rheumatism,  furun- 
culosis,  uraemia,  diabetes,  but  none  has  come. 

On  the  other  hand,  who  could  have  hoped  that  it  would  help 
us  in  the  diagnosis  of  central  pneumonia,  of  deep-seated  sup- 
purations and  of  trichinosis,  or  in  the  prognosis  of  relapsing 
fever  or  of  pneumonia? 

There  are  probably  not  more  than  five  or  six  diseases  in 
which  the  blood  examination  gives  us  the  diagnosis  ready-made, 
but  there  is  a  very  considerable  number  of  conditions  in  which 
the  blood  examination  will  help  us  to  make  it.  Not  pathogno- 
inonic  signs,  but  links  in  a  chain  of  evidence  are  what  we  are  to 
expect  from  blood  examination.  Yery  often  the  simple  discov- 
ery that  the  blood  is  normal  may  be  a  fact  of  the  greatest  value 
in  diagnosis. 

On  the  whole  it  seems  to  me  that  the  examination  of  the 
blood  gives  evidence  similar  in  kind  and  not  much  inferior  in 
value  to  that  obtained  by  examination  of  the  urine.  Both 
methods  of  examination  give  us  (a)  a  ready-made  diagnosis  in 
a  few  diseases ;  (b)  side  lights  on  a  good  many  obscure  condi- 
tions ;  and  (c)  the  frequently  great  assistance  of  a  negative  re- 
port. In  certain  wards  of  the  Massachusetts  ^General  Hospital 
it  has  been  for  some  years  the  rule  to  examine  the  blood  of 
every  patient  as  a  matter  of  routine  at  the  time  of  entrance.  In 
a  small  proportion  of  cases  this  gave  negative  evidence  only ;  in 
a  much  larger  proportion  it  materially  assisted  in  the  making  of 
a  diagnosis. 


4  INTRODUCTION. 

Improvements  in  technique  have  lessened  the  labor  and  in- 
creased the  accuracy  of  blood  examination.  The  most  important 
facts  about  the  blood  of  nearly  every  case  can  be  obtained  by 
a  practised  observer  in  fifteen  minutes.  The  experiments  of 
Beinert  and  others  have  shown  that  with  due  care  no  error  suffi- 
cient to  mislead  judgment  need  occur. 

The  blood  is  the  only  tissue  that  we  can  study  easily  during 
the  life  of  the  patient.  Its  relations  to  all  other  tissues  are  such 
that  it  is  typical  of  them  all  in  a  way  that  no  other  tissue  is,  act- 
ing on  all  and  being  acted  on  by  all.  As  yet  we  have  studied 
chiefly  its  morphology,  and  from  that  single  aspect  obtained 
most  of  the  clinically  valuable  information  which  we  possess 
about  it.  But  the  field  of  the  blood  chemistry  is  in  many  re- 
spects even  more  promising  at  the  present  time,  and  there  seems 
reason  to  believe  that  the  study  of  the  blood  is  still  in  its  in- 
fancy and  will  take  a  higher  place  in  the  future  as  an  aid  to  diag- 
nosis, prognosis,  and  treatment. 

Like  all  methods  of  physical  examination  it  has  especial  use- 
fulness when  we  cannot  communicate  with  a  patient,  either  by 
reason  of  his  unconsciousness,  stupidity,  or  insanity,  or  because 
he  speaks  no  widely  used  language.  In  such  cases  the  detec- 
tion of  marked  anaemia,  leucocytosis,  a  typhoid  serum-reaction, 
or  a  malarial  organism  may  be  of  great  assistance.  Malinger- 
ing is  made  more  difficult  by  it,  and  in  the  differentiation  of 
organic  from  functional  disease  it  is  often  very  helpful.  There 
is  no  febrile  disease  on  which  it  may  not  throw  light. 

The  evidence  for  these  and  many  other  aids  furnished  by 
the  blood  examination  in  clinical  work  is  given  in  the  later 
chapters  of  this  work. 


PART  I. 

METHODS     OF     CLINICAL     EXAMINATION     OF 
THE    BLOOD. 


CHAPTER  I. 

CONFINING  ourselves  to  the  clinically  available  processes  by 
which  we  can  gain  information  of  diagnostic  or  prognostic 
value,  blood  examination  at  the  present  time  embraces  eight 
processes. 

1.  Examination  of  the  fresh  blood  (with  or  without  a  warm 
stage). 

2.  Counting  the  red  and  the  white  corpuscles. 

3.  Estimation  of  the  relative  volumes  of  corpuscles  and  plasma 
by  centrifugalizing  the  blood. 

4.  Estimation  of  the  amount  of  coloring  matter. 

5.  Estimation  of  the  specific  gravity  of  the  blood. 

6.  Examination  of  dried  and  stained  specimens. 

7.  Bacteriological  examination  of  the  blood. 

8.  Examination  of  the  serum.1 

To  describe  these  processes  in  detail  is  the  purpose  of  the 
next  chapters. 

I.  EXAMINATION  OF  THE  FRESH  BLOOD. 

(a)  Obtaining  the  blood  by  puncture.  In  all  the  processes 
about  to  be  described,  except  the  bacteriological  examination, 
the  first  step  is  as  follows : 

Wipe  the  lobe  of  the  patient's  ear  with  a  damp  cloth  and 
then  rub  it  with  a  dry  one.  This  serves  to  remove  gross  dirt 
and  also  to  make  the  tissues  liypersemic,  so  that  a  slight  punc- 
ture will  draw  blood.  Attempts  to  sterilize  the  skin,  or  washing 
it  with  alcohol  and  ether,  are  unnecessary. 

Use  a  three-sided  (bayonet-pointed)  surgical  needle  or  a  small 
lancet — a  sewing  needle,  even  a  sharp  one,  gives  more  pain  and 
1  See  Chapter  xiii.  of  Book  II. 


6  CLINICAL   BLOOD    EXAMINATION. 

draws  less  blood  from  a  given  depth  of  puncture.  The  needle 
need  not  be  sterile.  In  several  thousand  blood  counts  made  at 
the  Massachusetts  General  Hospital  since  1893  the  needles  have 
never  been  sterilized  and  no  signs  of  sepsis  have  been  seen  in 
any  case. 

Possibly  this  is  due  in  part  to  the  fact  that  the  next  step  in 
the  process  after  the  puncture  has  been  made  is  always  to  wipe 
away  four  or  five  successive  drops  as  they  emerge,  which  serves 
not  only  to  get  the  blood  flowing  freely,  but  also  to  wash  the  ear 
in  its  own  blood. 

Jhe  puncture  is  best  made  into  the  lower  surface  or  edge  of 
the  lobe,  which  is  steadied  with  the  fingers  of  the  left  hand.  A 
very  quick  stroke  gives  least  pain,  the  hand  rebounding  like  a 
piano  hammer.  If  the  skin  of  the  lobe  is  stretched  tight  with 
the  fingers  of  the  left  hand  so  that  no  "  give"  is  possible,  the 
quick  puncture  gives  hardly  any  pain.  I  have  repeatedly  taken 
blood  from  a  sleeping  child  without  waking  it.  What  hurts  the 
patient  is  the  mistaken  tenderness  that  slowly  presses  the  needle 
through  the  skin.  The  puncture  must  be  deep  enough  to  make 
the  blood  flow  freely  and  without  pressure,  after  it  is  once 
started  by  pressing  out  a  few  drops.  Blood  squeezed  out  with 
pressure  should  never  be  used  for  counting,  as  it  is  likely  to  be 
considerably  diluted  with  fluid  pressed  out  of  the  neighboring 
tissues.  If  the  skin  is  moderately  thin  and  the  ear  easily  made 
hyperaemic,  a  puncture  one-eighth  of  an  inch  deep  is  sufficient. 
With  thick,  bloodless  skin  it  may  be  necessary  to  go  in  one- 
quarter  or  one-third  of  an  inch — never  more.  Beware  of  bleeders. 
I  have  seen  bleeding  from  a  puncture  made  for  a  blood  count 
which  could  not  be  checked  for  three-quarters  of  an  hour.  It  is 
always  safer  to  ask  after  a  history  of  haemophilia  as  a  matter  of 
routine  before  taking  blood,  just  as  one  asks  after  false  teeth 
before  etherizing.  If  there  is  a  history  of  haemophilia,  a  mere 
touch  of  the  needle  point  will  give  us  all  the  blood  we  need 
without  embarrassing  us  with  a  troublesome  hemorrhage. 

There  is  no  question  as  to  the  superiority  of  the  ear  over 
the  finger  for  drawing  the  drop.  The  ear  is  less  sensitive  than 
the  finger,  and  a  slighter  puncture  gives  us  all  the  blood  we 
need.  Moreover,  it  is  a  distinct  advantage,  especially  in  chil- 
dren, that  the  patient  cannot  watch  the  puncture  of  the  ear,  or 
the  preparations  for  making  it,  and  cannot  easily  withdraw  the 


METHODS   OF   CLINICAL   EXAMINATION.  7 

part.  A  sleeping  patient  often  needs  to  be  roused  to  get  at  his 
finger,  while  his  ear  is  usually  easily  accessible  above  the  bed 
clothes.  Again,  the  absence  of  any  bony  prominence  against 
which  to  press  makes  us  less  likely  to  use  too  much  pressure 
than  if  we  puncture  the  finger. 

When  one  is  making  frequent  examinations  of  the  blood  of  a 
sensitive  person,  as  in  pneumonia,  these  details  are  of  real  im- 
portance, and  in  cases  of  pernicious  anaemia  in  which  the  pre- 
vious attempts  to  get  blood  from  the  finger  had  been  absolute 
failures,  I  have  found  no  difficulty  in  getting  it  from  the  ear.  In 
this  disease  the  advantages  of  the  ear  over  the  finger  are  pecu- 
liarly great. 

Spreading  the  Blood. 

(b)  When,  after  wiping  away  the  first  four  or  five  drops,  a 
good-sized  drop  exudes  spontaneously,  touch  the  centre  of  a 
perfectly  clean  cover-glass  against  the  ^^^ 

summit    of  the  drop  without  touching         / ______f~~ 

the    skin  itself  at  all,   and    drop   the       /  jN>^ 

cover-glass    face    downward    upon    a     /  / 

slide  so  that  the  force  of  the  impact         """-— •— -*^--^ 

will  help  to  spread  the  drop  of  blood  r      

thinly  and  evenly  between  slide  and  \L        ) 

cover.     It  is  recommended  by  Ehrlich 

and  others    to    hold   the    cover-glass  FlG-  ^--^oper  Method  of  HOW- 

.,,    £  ,      ,   ,,  ,  .  ing  a  Cover  Glass. 

with  iorceps,  but  there  is  no  harm  in 

holding  it  with  the  fingers,  provided  we  avoid  touching  either 

of  its  surfaces,  i.e.,  hold  it  always  as  in  Fig.  I.1 

Slide  and  cover  must  be  perfectly  clean,  else  the  blood  will 
not  spread  out  in  a  layer  thin  enough  to  avoid  the  corpuscles 
overlying  each  other  so  that  not  one  of  them  is  clearly  seen. 
Further,  as  dirt  simulates  fairly  closely  some  of  the  pathological 
appearances  for  which  we  are  on  the  lookout,  its  presence  on  the 
slide  leads  to  loss  of  time  or  to  mistaken  conclusions.  Cover- 
glasses,  as  they  come  from  the  shops,  may  be  coated  with  a 
substance  not  easily  to  be  removed.  To  get  them  really  clean 

1 1  am  not  unmindful  of  Ehrlich's  warning  that  the  moisture  of  the 
fingers  spoils  the  specimen  ;  but  in  practice  I  do  not  find  it  to  be  true  ex- 
cept as  regards  the  margin  of  the  film,  the  good  preservation  of  which  is 
not  essential. 


CLINICAL   BLOOD    EXAMINATION. 

nothing  is  so  simple  as  or  more  effective  than  soap  and  water. 
After  several  years'  use  of  the  method  of  cleaning  usually  ad- 
vised (viz.,  strong  mineral  acid,  followed  by  alcohol  and  then  by 
ether),  I  have  become  converted  to  the  use  of  plain  soap  and 
water  as  the  best  and  simplest  way  of  cleaning  slides  or  cover- 
glasses.  Kub  soap  over  every  part  of  the  glass,  wash  it  off  thor- 
oughly with  water,  and  polish  it  with  a  clean  handkerchief 
(most  towels  are  apt  to  leave  a  scrap  of  lint  on  the  glass) . '  If 
slide  and  cover  are  perfectly  clean,  are  held  as  in  Fig.  1,  and  al- 
lowed to  touch  only  the  summit  of  the  blood  drop  and  not  the 
skin,  the  blood  will  spread  out  properly  between  them,  and  no 
pressure  on  the  cover-glass  will  be  needed  to  make  the  layer  of 
corpuscles  thin  enough.  Pressure  is  undesirable,  as  it  often 
makes  all  sorts  of  artefacts  in  the  preparation  and  hastens  cre- 
nation  of  the  red  corpuscles.  Better  results  are  obtained  if 
slide  and  cover  are  warmed  just  before  using. 

Prevention  of  Cell-Death. 

Slides  so  prepared  are  usually  best  examined  with  a  one- 
twelfth  oil-immersion  lens.  As  a  rule  they  keep  long  enough 
for  purposes  of  examination  without  any  further  precautions, 
but  if  we  desire  to  keep  the  blood  fresh  and  uncoagulated  for  a 
longer  period,  it  is  best  to  exclude  air  in  this  way :  Paint  upon 
the  slide  with  vaseline,  cedar  oil,  or  any  gummy  substance  a 
hollow  square  or  ring  of  about  the  size  of  the  cover-glass,  so 
that  when  the  latter  with  its  drop  of  blood  is  put  down  upon 
the  slide  the  drop  will  spread  out  inside  the  ring  of  oil,  which 
seals  the  margins  of  the  cover-glass  to  the  slide.  Specimens  so 
prepared  will  keep  for  many  hours  unchanged,  and  without  cre- 
nation  or  coagulation,  if  the  weather  is  warm  or  if  the  slide  be 
kept  in  a  warm  place. 

In  examining  blood  suspected  of  containing  malarial  para- 
sites it  is  sometimes  useful  to  put  the  whole  microscope  into 
one  of  the  warming  apparatuses  devised  for  the  purpose.  This 
is  better  than  any  of  the  various  kinds  of  warm  stage  in  use,  but  in 
clinical  work  there  is  rarely  if  ever  any  need  for  artificial  heating 

1  Further  experience  has  convinced  me  that  water  alone  is  generally 
sufficient,  provided  the  polishing  is  thorough.  Tissue  paper  is  very  useful 
for  polishing  cover-glasses.  After  polishing,  it  is  well  to  pass  them  through 
a  Bunsen  or  alcohol  flame  once  or  twice. 


METHODS   OF   CLINICAL   EXAMINATION.  9 

apparatus  of  any  kind,  provided  the  room  and  the  slide  are 
warm. 

What  Can  be  Learned  from  Fresh  Blood. 

Examination  of  the  fresh  blood  by  the  method  just  described  is 
the  best  way  known  for  ascertaining  the  presence  or  absence  of — 

1.  The  Plasmodium  malariae. 

2.  The  Spirochaete  of  relapsing  fever. 

3.  The  Filaria  sanguinis  hominis. 

4.  Rouleaux  formation  among  the  red  cells. 

It  is  also  a  quick  and  convenient  method  of  finding  out  with 
approximate  accuracy : 

(a)  Whether  the  blood  contains  an  increased  amount  of  fibrin ; 

(b)  "Whether  any  considerable  anaemia  or  leucocy tosis '   is 
present ; 

(c)  Whether  or  not  the  amount  of  haemoglobin  in  the  red 
cells  is  much  decreased; 

(d)  Whether  the  red  corpuscles  are  deformed ; 

(e)  Whether  the  "  blood  plates"  are  increased  or  not. 

A  practised  observer  can  also  make  a  diagnosis  of  leukaemia  by 
this  method  in  most  cases,  but  here  mistakes  may  easily  occur. 

So  much  can  sometimes  be  learned  from  a  specimen  pre- 
pared in  this  very  quick  and  easy  way  that  it  should  be  as  much 
a  matter  of  routine  as  a  urine  examination.  But  in  order  to  get 
any  information  from  such  a  preparation  we  must  previously 
have  familiarized  ourselves  with  the  appearance  of  normal  blood 
under  such  conditions — with  the  size,  shape,  color,  and  refrac- 
tions of  the  red  cells,  white  cells,  and  blood  plates  and  their  ratio 
to  one  another,  and  with  the  great  variety  of  curious  phenomena 
to  be  seen  as  a  drop  of  blood  gradually  dries  up  between  slide 
and  cover.  No  book  can  teach  this:  it  must  be  learned  by 
actual  experiment. 

Some  of  the  commoner  sources  of  error  will  be  referred  to 
later.  Here  I  will  mention  only  the  Brownian  movement  in  the 
protoplasm  of  the  corpuscles,  to  be  distinguished  clearly  both 
from  the  amoeboid  movements  of  the  leucocytes  or  of  the  malarial 
parasite  and  also  from  the  irregular  contractions  of  the  dying 

1  More  accurately  it  is  only  the  ratio  of  red  to  white  corpuscles  that 
we  can  determine,  and  when  the  red  are  very  much  diminished  in  num- 
ber we  may  be  deceived  into  supposing  that  the  white  are  increased. 


10  CLINICAL   BLOOD    EXAMINATION. 

protoplasm,  which  give  rise  to  pseudo-amoeboid  motions  in  the 
crenated  points  of  normal  red  cells  or  in  the  irregular  projections 
of  corpuscles  deformed  by  disease  (vide  infra) . 

For  a  more  detailed  description  of  normal  red  corpuscles, 
white  corpuscles,  and  blood  plates  the  reader  is  referred  to 
Part  II. 

An  account  of  the  pathological  changes  to  be  observed  in  the 
fresh  blood  will  be  given  in  later  chapters. 


CHAPTEE  II. 


COUNTING  THE  CORPUSCLES. 

I.  THE  Thoma-Zeiss  counter. 

II.  Durham's  modified  counter. 

I.  Out  of  the  many  instruments  devised  for  this  purpose 

that  of  Thoma-Zeiss  is  much 
the  most  commonly  used.  In 
the  use  of  this  instrument 
there  are  five  steps  or  stages : 

1.  Puncturing  the  ear. 

2.  Diluting     and     mixing 
the  blood  thus  obtained. 

3.  Adjusting  a  drop  of  di- 
luted blood  in  the  counting 
chamber. 

4.  Counting  the  corpuscles, 

5.  Cleaning  the  pipette. 

To  count  the  white  corpus- 
cles, a  different  instrument  is 
often  used  from  that  em- 
ployed for  the  red. 

The  technique  is  nearly 
the  same  for  both  instru- 
ments, but  for  clearness'  sake 
I  shall  describe  them  sepa- 
rately. To  save  time  I  shall 
call  the  small-bore  pipette 
used  for  red  corpuscles  (Fig. 
2,  A}  the  "red  counter,"  and 

FraS.-Thoma-Zeiss  Pipettes.    A.  For  red  cor.    the    ^rge-bore     pipette    (Fig. 
puscles;  B,  for  white  corpuscles.  2,  B)   the  "  white  Counter." 


COUNTING  THE  BED  CORPUSCLES. 

(a)  After  puncturing  the  ear  as  above  described,  and  as  soon 
as  the  blood  is  flowing  freely,  put  the  point  of  the  "  red  counter" 


12  CLINICAL   BLOOD    EXAMINATION. 

into  the  drop  as  it  emerges  from  the  ear,  and  by  sucking  gently 
on  the  rubber  tube  attached  to  the  other  end,  draw  up  blood  to 
the  mark  0.5  on  the  pipette.  It  is  convenient  to  rest  the  end 
of  the  pipette  on  the  thumb  as  shown  in  Fig.  3.  It  needs  some 

practice  to  stop  exactly  at  the  mark, 
but  if  we  happen  to  draw  the  blood 
up  a  little  past  the  mark  0.5  no  con- 
siderable error  results,  provided  we 
draw  the  column  down  again  to  the 
mark  by  tapping  the  point  of  the 
pipette  on  a  towel,  and  provided  also 
that  the  instrument  is  perfectly  clean 
and  dry.  The  aim  and  intention, 
however,  should  always  be  to  stop 

FIG.    3.-Method    of    Resting  J 

Point  of   Pipette  on  tne      exactly  at  the  mark  0.5,   and  with  a 

Thumb  while   Sucking  in      j^tle  practice    we  can  do    it,   except 

with  nervous    or    delirious    patients, 

and  those  who  carelessly  move  the  head  just  at  the  critical 
moment.  With  such  patients  we  usually  have  to  content  our- 
selves with  drawing  the  blood  a  little  beyond  the  mark  0.5 
and  then  drawing  it  down  again  to  the  mark  as  above  de- 
scribed. 

Diluting  the  Blood. 

(V)  The  bottle  of  solution  to  be  used  for  diluting  the  blood 
should  be  ready  uncorked  at  the  bedside.  Of  the  many  solu- 
tions suggested  by  various  authors  none  is  better  than  Gaivers', 
the  formula  for  which  is  as  follows : 

Sodii   sulphat.,   .         .         .         ...  gr.  112 

Acid,  acetic. ,      .         .         .         .        .         .    3  v. 

Aquse,  ..' §  iv. 

Toisson's  solution  is  also  very  useful  and  stains  the  white 
corpuscles  so  that  they  can  be  easily  distinguished  from  the  red. 
Its  composition  is  as  follows : 

Methyl  violet,  5  B,. 025  gm. 

Sod.  chlor., 1.000    " 

Sod.  sulph 8.000     " 

Neutral  glycerin, 30.000cm. 

Aquse  destill. , 160.000cm. 


COUNTING   THE   CORPUSCLES.  13 

We  must  wait  about  ten  minutes  after  mixing  before  the  leu- 
cocytes are  fully  stained.  Except  for  this  delay,  the  only  diffi- 
culty of  this  solution  is  that  it  is  rather  difficult  to  clean  the 
pipette  after  using  it.  If  the  white  cells  are  counted  with  an- 
other pipette  the  staining  fluid  can  be  as  well  dispensed  with. 

Into  a  bottle  of  one  of  these  solutions,  ready  at  the  bedside, 
the  point  of  the  pipette  is  to  be  plunged  as  soon  as  the  blood 
has  been  drawn  up  to  the  point  0.5  and  the  outside  of  the  pipette 
wiped  clean  of  blood.  Suction  is  then  exerted  through  the 
rubber  tube  the  instant  the  point  of  the  pipette  is  below  the  sur- 
face of  the  diluting  solution.  This  suction  is  continued  until 
the  diluted  blood  has  filled  the  bulb  of  the  pipette  and  gone 
past  it  up  to  the  point  marked  101.  It  is  not  difficult  to  stop 
at  this  point,  provided  the  pipette  is  perfectly  clean  and  dry 
inside.  Otherwise  it  is  impossible.  Should  any  mishap  oc- 
cur at  this  point,  the  whole  process  must  be  begun  over  again 
after  carefully  cleaning  and  drying  the  pipette.  If  no  acci- 
dent happens  and  the  mixture  is  sucked  up  to  and  not  past  the 
mark  101,  we  have  diluted  the  blood  with  two  hundred  times 
its  bulk  of  neutral  solution.  If,  instead  of  drawing  the  blood 
up  to  the  mark  0.5  we  draw  it  as  far  as  the  point  marked 
1,  and  then  dilute  as  above  described,  the  mixture  will  be 
1  to  100.  Some  observers  habitually  use  this  dilution.  The 
objections  to  it  are :  (1)  That  if  the  blood  is  accidentally  drawn 
up  too  far  (i.  e. ,  past  the  mark  1)  we  cannot  draw  it  down  again 
but  must  painfully  clean  and  dry  out  the  pipette  (see  below, 
p.  16)  and  repeat  the  process.  (2)  If  the  blood  contain  ap- 
proximately the  normal  number  of  corpuscles,  they  will  be  so 
crowded  when  adjusted  on  the  ruled  surface  of  the  disc  A  that 
it  is  more  difficult  to  count  them.  If  we  use  another  pipette  for 
the  white  corpuscles  the  dilution  of  1 : 100  has  no  advantage  to 
counterbalance  these  drawbacks. 

While  sucking  in  the  diluting  solution,  it  is  well  to  roll 
the  pipette  on  the  long  axis  with  the  fingers  of  the  hand  which 
holds  it  in  the  diluting  fluid.  This  mixes  the  blood  instantly 
and  prevents  any  of  it  from  floating  on  the  top  of  the  solution 
and  thereby  coming  up  undiluted  into  the  narrow  portion  above 
the  bulb  of  the  pipette,  where  it  might  possibly  escape  thor- 
ough mixing.  * 

*Care  must  be  taken  that  no  saliva  finds  its  way  through  the  rubber 
tube  and  into  the  pipette.  Never  blow  through  the  rubber  tube. 


14  CLINICAL   BLOOD    EXAMINATION. 

Next  we  thoroughly  mix  the  blood  and  diluting  fluid  by 
shaking  and  rolling  the  pipette,  its  ends  being  closed  by  the 
fingers.  The  little  glass  ball  within  the  bulb  helps  this  process 
materially.  A  minute's  brisk  rolling  and  shaking  is  as  good  as 
five  minutes',  as  I  have  convinced  myself  by  many  experiments, 
and  the  distribution  of  the  corpuscles  throughout  the  mixture  is 
very  even,  provided  there  is  no  delay  in  proceeding  to  the  next 
step,  Viz. : 

(c)  Adjusting  a  Drop  of  Diluted  Blood  in  the  Counting  CJiamber. 
— Remove  the  rubber  tube  from  the  pipette  and  blow  out  the  por- 
tion of  diluting  solution  which  last  entered  the  pipette,  and  which 
consequently  has  not  been  thoroughly  mixed  with  the  blood  in 
the  bulb.  Five  or  six  drops  should  be  blown  out  before  any  is 
used  for  examination.  Next  put  upon  the  surface  of  the  couDter 
(A,  Fig.  4)  a  drop  of  such  size  that  when  the  cover-glass  (B) 


\    x i 


V  \c 


FIG.  4.— Thoma-Zeiss  Counting  Slide.    A,  Ruled  disc  ;  B,  cover-glass  ;  C,  moat. 

is  let  down  over  it  the  whole  of  the  disc  A  is  covered  with  the 
drop  without  any  being  spilled  into  the  "moat"  (C)  around  it. 
Just  how  large  such  a  drop  should  be  can  only  be  learned  by 
practice.  It  is  not  literally  necessary  thai  exactly  the  whole 
disc  A  should  be  covered,  provided  nine-tenths  of  it  is  covered, 
but  any  spilling  over  into  the  "moat"  (C)  entails  serious  error. 
After  the  cover-glass  has  been  let  down  upon  the  drop,  we 
should  be  able  (provided  the  whole  instrument  is  clean)  to  see 
concentric  rainbow  rings  between  the  cover-glass  and  the  body 
of  the  instrument.  These  are  known  as  Newton's  rings.  A 
little  pressure  with  a  needle  on  the  cover-glass  will  often  bring 
them  out  if  they  do  not  at  once  appear,  but  they  must  remain 
visible  after  the  pressure  is  taken  off.  Otherwise  we  know  that 
fchere  must  be  some  dirt  or  dust  under  the  cover-glass  prevent- 
ing its  settling  exactly  into  position,  and  this  will  cause  error  in 

1  If  we  have  to  pause  before  going  on  to  the  next  step,  we  must  take 
care  to  roll  and  shake  the  pipette  again  when  ready  to  proceed. 


COUNTING   THE   COKPUSCLES. 


15 


the  count,  though  not  a  very  considerable  error  in  most  cases. 
(To  see  Newton's  rings  we  should  get  our  eyes  near  to  the  level 
of  the  counting  chamber  so  that  the  light  from  window  or  lamp 
is  reflected  from  the  surface  of  the  cover-glass.) 

If  the  above  conditions  are  not  all  fulfilled  the  instrument 
should  be  washed  and  another  drop  tried,  after  shaking  the 
pipette  and  blowing  out  a  few  drops  as  before. 

The  cover-glass  must  be  let  down  as  soon  as  possible  after 
the  drop  has  been  put  on  the  disc  A,  and  before  the  corpuscles 
have  time  to  settle.  It  is  best  to  let  it  down  with  a  needle  as  in 
mounting  microscopic  specimens. 


Counting. 

(d)  After  waiting  two  or  three  minutes  so  that  the  corpuscles 
may  settle  thoroughly  upon  the  space  ruled  off  on  the  disc  A, 

A 


O.lOOmtn. 


4005 


C.Zeiss 

Jena 


FIG.  5. — Thoma-Zeiss  Counting  Slide.    A^  Ruled  disc. 

the  counting  is  begun,  using  preferably  an  objective  5  of  Leitz 
or  D  of  Zeiss  and  a  No.  1  or  2  eyepiece. 

The  ruled  space  on  the  surface  of  the  counter  (A,  Fig.  5). 
is  divided  into  four  hundred  squares,  every  group  of  sixteen 
squares  being  enclosed  in  double  lines  to  make  it  easier  to  know 
how  many  squares  we  have  counted  (see  Fig.  6).  Including 
the  squares  with  double  lines  we  have  a  group  containing  thirty- 
six  small  squares,  a  group  convenient  to  count  at  one  time  as  it 
just  about  fills  the  field  of  the  objective  Leitz  Na.  5,  or  Zeiss  D 
with  a  No.  2  eyepiece. 

To  avoid  considerable  error  we  should  count  the  corpuscles 


16 


CLINICAL   BLOOD   EXAMINATION. 


in  five  fields  of  thirty -six  squares  each,  such  as  is  shown  in  Fig. 
6,  taking  the  fields  in  various  parts  of  the  whole  ruled  space. 
The  instrument  should  then  be  washed*  and  the  whole  process 
repeated  with  a  second  drop.  If  the  count  of  the  second  drop 
differs  widely  from  that  of  the  first,  a  third  drop  should  be 
counted  and  the  average  taken  of  those  two  which  are  most 
nearly  alike.  Thus  at  least  three  hundred  and  sixty  small 
squares  should  be  counted ;  with  such  a  number  the  error  is  not 
over  three  per  cent  for  practised  observers.2  In  normal  blood 
this  means  counting  about  2,160  corpuscles,  as  six  or  seven  to  a 
small  square  is  about  the  normal  average  when  we  are  using  a 
dilution  of  1 : 200  such  as  has  been  described  (twelve  to  fourteen 
cells  per  square  in  a  dilution  of  1 : 100). 

Among  the  difficulties  encountered  in  counting  is  the  pres- 
ence of  a  few  corpuscles  on  or  touching  one  or  more  of  the  lines 
bounding  the    space   to 
be    counted.     Shall  we 
count  these  out  or  in? 

In  counting,  for  in- 
stance,  a  field  like  that 
in  Fig.  6,  what  are  we 
to  do  with  the  cells 
which  sit  astride  the 
lines  AA,  BB,  etc.  ? 

To  get  round  this 
difficulty,  it  is  best  to 
make  it  a  rule  to  count 
in  all  the  corpuscles  on 
or  touching  some  two  of 
the  boundary  lines  (e.g., 
AA  and  BB)  and  to 
take  no  notice  of  any 
cell  on  or  touching  the 
lines  CC  and  DD.  In  this  way  the  exclusions  just  balance  the 
inclusions.  Of  course  all  cells  within  these  outer  boundary 
lines  are  to  be  counted  whatever  their  position. 

1  Use  only  water — alcohol  dissolves  the  cement  which  holds  the  ruled 
disc  in  place. 

2  See  Reinert's  "Zahlung  der  Blutkorperchen,"  Leipzig,  1891,  p.  48  et 


0° 

o  c 

0 

o 

o 

o 

O      r 
0° 

°oo 
>o  o 

O  6 
0    0 

0     0 

o 

o 

0 

o 

ooo 

°n 

,      °o 

0        0 

o0o 

o 

0 

0 

0  6 

**J 

0  0 

0     O 

0 

0 

°0° 

O 

00 

o 

0 

oo 
o  o 

<'. 

0 

o 

O  o 
0  0 

0   °° 

0  0 

0     0 

00 

o 

0      0 

00 

o 

0 

0 

0     °° 
0   0 

o  o 

Oo 
o 

o 
o 

°00 
)    OO  O 

o  ° 

°°0°° 

0°0 
°0 

o 
o 
o 

0 

o 

0 

00° 

o  < 

0 

0°°°' 

°0 

°0 

0°0 

0         0 
O  O  o 

oo 

o 
o 
o 

0 

o 

0  O 

O  o 

v 

°0 

o°u 

°o  . 

0  Q 

0 

0 

o 

O 

o 

°0 

o°o 

0     ° 

°o 

o° 

0 

o 

w  0 

0  0 

o 

0 

0 

o 

0 

0     q 

o  o 

0         0 
0    0 

l°o° 

0  o 

o 

0 

0 

o°o 

0 

FIG.  6.— Field  of  Thirty-six  Squares  on  Ruled  Disc  of 
Thoma-Zeiss  Counter  Covered  with  Normal  Blood 
Diluted  Two  Hundred  Times. 


COUNTING   THE   CORPUSCLES. 


17 


Beyond  this  the  details  must  be  settled  by  each  man  for  him- 
self. My  own  habit  is  to  count  through  the  squares  in  the  order 
indicated  by  the  track  of  the  serpentine  arrow  in  the  accompany- 
ing Fig.  7,  and  to  count  by  twos  or  threes. 

A  movable  stage  makes  the  counting  easier,  especially  for  be- 
ginners. Either  natural  or  artificial  light  may  be  used,  with  a 
small  aperture  diaphragm,  and  if  the  instruments  are  clean  and 
the  diluting  solution  fresh  and  free  from  sediment, l  there  is  no 
difficulty  in  deciding  how  many  cells  each  square  contains,  and 
no  extraneous  fragments  to  be  excluded.  We  must  distinguish 
the  white  corpuscles  from  the  red,  not  by  their  size  but  by  their 
stain  if  Toisson's  solution  is  used,  otherwise  by  their  peculiar 
shining  look  when  the  lens  is  drawn  up  so  as  to  put  the  red 
cells  slightly  out  of  focus.  The  blood  plates  are  not  noticeable 
and  lead  to  no  errors. 

When  the  number  of  corpuscles  in  360  squares  has  been 

counted  the  number  is 
divided  by  360  and  multi- 
-  plied  by  800, 000  (i.e.,  by 
200  to  make  up  for  dilu- 
tion and  then  by  4,000 
because  each  square  is 
equivalent  to  J^VTF  of  a 
cubic  millimetre),  which 
gives  us  the  number  of 
_  corpuscles  per  cubic  mil- 
limetre. 

These  figures  need  not 
-  be  committed  to  memory, 
~~for  we  have  marked  on 
the  instruments  used  all 

FIG.  ?.-The  Arrow  Indicates  the  Order  in  which  the  tllQ  data  necessary  for  the 

squares  are  counted.  calculation,  i.e.,  the  dilu- 

tion figures  on  the  pipette 

and  the  area  and  depth  of  a  single  square  on  the  counting  slide. 

(e)  The  importance  of  cleaning  the  pipette  as  soon  as  the 

counting  is  done  is  so  great  that  it  should  be  reckoned  as  one  of 

the  regular  steps  on  every  count.     First  water,  then  alcohol,  and 

1  Most  diluting  solutions  precipitate  or  accumulate  spores,  and  need  to- 
be  frequently  renewed  or  filtered. 

2 


18  CLINICAL   BLOOD    EXAMINATION. 

lastly  ether  must  be  sucked  into  the  pipette  and  brought  into 
contact  with  every  part  of  the  bulb  and  tube.  After  this  air 
must  be  sucked  or  pumped  through  the  tube  until  it  is  per- 
fectly dry  and  the  glass  ball  will  roll  about  freely  in  the  bulb 
without  sticking  anywhere. 

These  precautions  take  but  two  or  three  minutes,  and  if  they 
are  omitted  and  the  blood  dries  in  the  pipette,  it  may  take 
several  hours'  work  to  get  it  clean.  Further,  if  it  is  not  thor- 
oughly dried  after  cleaning,  the  mixing  of  the  blood  when  it  is 
used  next  cannot  be  done  accurately. 

The  first  three  steps  of  the  above  process  (i.e.,  the  obtaining, 
diluting,  and  mixing  of  the  blood)  must  be  done  as  swiftly  as  is 
compatible  with  accuracy,  but  when  once  the  blood  is  mixed  in 
the  pipette  it  can  be  kept  there  indefinitely  and  counted  at 
leisure.  None  of  the  corpuscles  are  destroyed  or  lost,  and  if  the 
bulb  is  thoroughly  rolled  and  shaken  up  whenever  we  are  ready 
to  count  the  blood,  no  error  results  from  keeping  it  twenty-four 
hours  or  more  in  the  pipette. 

It  is  not  necessary,  therefore,  to  carry  a  microscope  to  the 
patient's  house  or  bedside;  the  pipette  and  the  diluting  solution" 
are  all  that  we  need  to  take  with  us,  and  when  the  blood  is 
mixed  in  the  pipette,  the  latter 's  ends  can  be  closed  with  a 
rubber  band  and  the  blood  carried  home  and  counted  at  leisure. 
The  pipette  should  be  kept  approximately  horizontal  during  the 
transit. 

COUNTING  THE  WHITE  CORPUSCLES. 

To  make  a  reasonably  accurate  count  of  white  corpuscles, 
using  the  "  red  counter"  and  the  dilution  of  1 : 100  or  1 : 200,  we 
need  to  count  an  immense  number  of  squares,  far  more  than  was 
necessary  in  estimating  the  red  cells — in  fact,  at  least  ten  times 
the  whole  ruled  space.  It  is  therefore  far  quicker  and  more  ac- 
curate to  use  the  "  white  counter"  or  large-bore  pipette  with  a 
diluting  solution  which  renders  the  red  cells  invisible  and  leaves 
only  the  white  to  be  counted.  Such  a  solution  is  the  one-third 
of  one-per-cent.  solution  of  glacial  acetic  acid  in  water.  With 
this  the  white  corpuscles  stand  out  very  clearly  and  the  red  can 
barely  be  seen  at  all.  The  technique  is  the  same  as  that  already 
described,  with  the  following  exceptions : 

1.  The  drop  of  blood  needed  is  nearly  three  times  as  large 


COUNTING    THE   CORPUSCLES.  19 

as  that  used  in  the  "red  counter;"  it  is  about  as  big  as  can  be 
made  to  stay  on  the  ear  without  rolling  off. 

2.  The  bore  of  the  tube  being  large,  it  fills  and  empties 
more  readily.     Hence  our  suction  must  be  gentler,  and  it  is 
rather  harder  to  stop  exactly  at  the  mark  11.     For  the  same 
reason  the  diluted  blood  will  run  out  of  the  pipette  if  the  latter 
is  not  kept  nearly  horizontal,  and  the  bottle  of  diluting  solution 
should  accordingly  be  tipped  up  as  we  plunge  in  the  point  of 
the  pipette,  so  that  the  latter  is  depressed  as  little  and  for  as 
short  a  time  as  possible  before  suction  begins. 

3.  Instead  of  counting  separate  fields  of  thirty-six  squares 
each,  we  should  count  the  whole  ruled  space  and  then  repeat 
the  process  with  a  second  drop.     This  takes  never  over  fifteen 
minutes,  often  not  over  five,  and  is  very  accurate. 

The  advantages  of  this  pipette  are  obvious.  The  only  draw- 
backs are  its  expense  and  the  need  of  a  somewhat  deeper  and 
more  painful  puncture  to  get  blood  enough  for  it.  The  tech- 
nique is  not  at  all  difficult. 

Counting  Both  Red  and  White  Cells   With  the  Same  Pipette. 

We  may  avoid  buying  both  large-bore  and  small-bore  pipettes 
in  one  of  the  following  ways : 

1.  We  can  count  both  red  and  white  corpuscles  with  the  "  red 
counter. " 

2.  We  can  count  both  red  and  white  corpuscles  with  the 
"white  counter." 

The  reason  why  we  cannot  use  the  "  red  counter"  for  count- 
ing white  cells,  unless  modified  in  some  way,  is  that  in  the 
whole  ruled  surface  of  the  counting  chamber  not  more  than  three 
or  four  white  corpuscles  are  to  be  found  in  normal  blood  when 
diluted  two  hundred  times.  If  we  dilute  less,  we  cannot  see  the 
cells  distinctly  because  they  are  so  crowded.  If  we  find,  say, 
three  white  corpuscles  as  the  number  to  be  used  as  a  basis  in 
calculating  the  number  of  white  cells  in  a  cubic  millimetre,  the 
chance  of  error  is  very  great,  the  multiplier  being  so  large 
(2,000)  and  the  multiplicand  so  small  (3). 

To  get  over  this  difficulty  we  may  utilize  the  cells  spread 
over  the  disc  of  the  counting  chamber  outside  the  ruled  space  in 
one  of  the  following  ways : 

(a)  By  measuring  the  field  of  the  objective  used.     The  writer's 


CLINICAL   BLOOD    EXAMINATION. 


objective,  No.  5  of  Leitz,  has  a  field  of  very  nearly  one-quar- 
ter of  a  square  millimetre  or  one-quarter  of  the  whole  ruled 
space.  Four  fields  of  this  lens,  taken  anywhere  outside  the 
ruled  space,  therefore,  contain  the  same  number  of  cells  as  will 
cover  the  whole  four  hundred  small  ruled  squares,  and  when 
we  have  counted  the  white  cells  in  a  series  of  four  fields  of 
this  lens,  we  have  accomplished  as  much  as  if  we  have  put  a 
fresh  drop  upon  the  counting  chamber  and  counted  all  the 
ruled  squares  over  again;  the  latter  process  is  tedious,  the 
former  very  quick.  Thus  it  is  my  practice  in  some  cases  to 
proceed  as  follows  (see  Fig.  8) :  Supposing  the  large  circle 
CCCC  to  represent  the  surface  of  the  small  disc  (A,  Fig.  4.) 
in  the  centre  of  the  counting  chamber,  and  AAAA  the  ruled 
squares  in  the  mid- 
dle of  this  disc,  four 
microscopic  fields 
are  taken  in  the  di- 
rection away  from 
the  centre  indicated 
by  circles  and  ar- 
rows in  the  figure. 
Starting,  say,  to  the  c 
right  of  the  ruled 
squares  with  the 
left  edge  of  the  mi- 
croscopic field  just 
touching  the  outer 
boundary  line  of  the 
squares,  count  all 
the  white  cells  to  be 
seen  in  the  field. 
Then  move  along  to  the  right  till  the  corpuscles  which  were  on 
the  extreme  right  of  the  first  field  have  gone  out  of  sight  to  the 
left.  Your  field  is  then  in  the  position  of  the  circle  marked 
2  (Fig.  8).  Count  all  the  white  cells  in  this  field  and  so  on 
for  four  fields.  With  my  objective,  four  such  fields  are  almost 
exactly  equal  to  the  whole  ruled  space  AAAA.  With  other  ob- 
jectives of  course  the  number  of  fields  is  different. 

When  we  have  counted  four  fields  in  each  of  the  four  direc- 
tions indicated  by  the  arrows  we  have  covered  as  much  ground 


COUNTING   THE   CORPUSCLES. 

as  if  we  have  put  four  successive  drops  on  the  slide  after  the 
first  one  and  counted  all  the  ruled  squares  in  each,  and  we  have 
saved  much  time  and  labor. 

(&)  Another  and  better  method  of  attaining  this  same  end  is 
as  follows:  Cut  out  of  black  cardboard  a  piece  of  the  shape 
shown  in  Fig.  9  and  of  such  a  size  that  it  will  fit  into  the  tube 
of  the  eyepiece — the  square  aperture 
allowing  a  space  of  just  one-quarter  of 
a  millimetre  (one  hundred  of  the  ruled 
squares)  to  be  seen  through  it  with  a 
given  objective  (say  Leitz  No.  5).  Four 
fields  as  seen  through  such  an  aper- 
ture can  then  be  counted  in  various 
parts  of  the  slide  outside  the  ruled 
space  as  explained  above. 

(c)  For  any  one  living  where  micro- 
scopic ruling  on  glass  can  be  done  at  a 

moderate  cost,  by  far  the  best  way  is  to  have  the  rest  of  the 
disc  A  (Fig.  5)  ruled  off  as  shown  in  Fig.  10.  Leitz  &  Zeiss 

a 


FIG.  9. 


FIG.  10.— Modified  Ruling  of  Thoma-Zeiss  Counting-chamber. 

now  make  to  order  instruments  so  ruled.  I  have  not  been  able 
to  hear  of  any  one  in  America  who  could  do  such  work  at  a 
moderate  expense. 


22  CLINICAL  BLOOD   EXAMINATION. 

(d)  We  may  work  out  mathematically  what  number  of 
squares  would  be  contained  on  the  whole  disc  were  it  all  ruled 
like  the  central  portion.  This  can  'be  done  with  the  aid  of  a 
micrometer  eye-piece  and  a  mechanical  stage.  There  is  some 
variation  in  individual  instruments,  but  as  a  rule  the  disc  out- 
side the  central  ruled  space  has  an  area  of  about  two  thousand 
of  the  small  squares. 

2.  We  may  use  the  "  white  counter"  for  red  corpuscles  in  the 
following  way :  Suck  up  blood  only  to  the  first  mark  up  from 
the  point  (i.e.,  one-fifth  of  the  usual  distance)  and  then  Gowers' 
or  Toisson's  solution  up  to  the  mark  11.  This  gives  a  dilution 
of  1 : 100,  and  in  anaemic  cases,  in  which  the  cells  are  not  very 
numerous,  answers  well.  The  same  pipette  can  then  be  care- 
fully cleaned  and  used  for  counting  white  cells  with  the  acetic 
acid  one-third  per  cent,  and  a  dilution  of  1 : 10  or  1 :  20. 

WTiatever  method  of  counting  white  corpuscles  is  adopted, 
we  ought  to  have  at  least  one  hundred  corpuscles  actually 
counted  to  use  as  the  multiplicand  of  our  computation.  A  single 
drop  from  the  white  counter  with  a  dilution  of  1 : 10  gives  us 
normally  about  seventy  white  corpuscles  in  the  four  hundred 
ruled  spaces,  and  by  repeating  the  process  with  a  second  drop 
the  result  may  be  made  reasonably  accurate.  This  was  the 
method  adopted  by  Rieder1  in  the  immense  number  of  counts 
made  by  him. 

II.  Durham's  Modified  Hcemocytometer. 

In  the  Edinburgh  Medical  Journal  for  October,  1897,  Herbert 
E.  Durham,  of  Cambridge,  England,  describes  a  self -filling 
capillary  pipette  which  has  considerable  advantages  over  the 
ordinary  Thoma-Zeiss  instrument.  The  account  of  the  device 
is  here  given  in  his  own  words. 

"  The  apparatus  entails  no  new  principle ;  it  is  rather  to  be 
considered  as  an  adaptation  of  a  number  of  details,  which  to- 
gether seem  to  present  some  advantages.  As  in  the  Gowers' 
instrument,  there  is  a  separate  capillary  pipette  for  measuring 
the  blood,  one  for  measuring  the  diluting  fluid,  a  mixing  vessel, 
and -the  counting  chamber.  A  few  words  may  be  said  about 
each  of  these. 

"  Capillary  Pipette. — There  is  an  obvious  advantage  in  the 

1 "  Beitrage  zur  Kenntniss  der  Leucocytosis, "  Leipzig,  1892  (Vogel). 


COUNTING   THE   CORPUSCLES.  23 

use  of  a  self-measuring  pipette.  It  cannot  go  wrong  by  acci- 
dent. Durham  has  availed  himself  of  the  pipettes  introduced 
by  Dr.  Oliver,  namely,  small  pieces  of  thick- walled  capillary 
tube — 5  and  10  c.mm.  in  capacity.  These  are  carefully  recali- 
brated by  the  makers  of  Dr.  Oliver's  instrument — The  Tinto- 
meter Company. 

"  There  is,  moreover,  another  important  advantage  attaching 
to  Dr.  Oliver's  pipette;  this  consists  in  the  readiness  with 
which  it  may  be  cleansed.  As  he  has  described,  all  that  is 
necessary  is  to  pass  a  piece  of  darning  cotton  by  means  of  a 
needle  through  the  bore  of  the  pipette.  All  the  adherent  serum, 
etc. ,  is  completely  removed  thereby.  Durham  generally  wets  the 
end  of  the  cotton  with  ether,  but  this  is  not  absolutely  necessary. 
In  passing  the  needle,  it  is  better  to  pass  it  into  the  pointed 
end,  in  case  it  is  not  withdrawn  perfect^  axially,  when  there  is 
a  liability  to  chip  the  thinner  unsupported  glass. 

"Any  one  who  has  worked  much  with  the  Thoma-Zeiss 
pipette  will  know  how  troublesome  it  is  to  clean,  especially 
when  a  number  of  observations  have  to  be  made  in  a  limited 
time.  Unless  it  is  frequently  cleaned  out  with  strong  acid, 
there  is  a  tendency  for  the  deposition  of  sticky  serum  remains 
which  interfere  with  true  readings. 

"For  use,  Dr.  Oliver's  pipettes  are  mounted  by  means  of  a 


FIG  11.— Cross-section  of  Durham's  Automatic  Blood-Pipette.  T,  Glass  tube  (like  that  of 
medicine-dropper) ;  JV,  rubber  nipple  (like  that  of  medicine-dropper) ;  p,  perforation 
in  the  nipple;  c,  Cork  holder,  perforated  by  capillary  pipette. 

small  cork  (c)  in  a  large  glass  tube  ( T),  which  is  provided  with  a 
rubber  nipple  (N),  having  a  lateral  perforation  (p)  (Fig.  11). 

"  The  mixing  vessel  consists  of  a  small  test  tube  (2f  X  yV  in- 
for  1  c.c.,  or  2fx|  in.  for  -J-  c.c.).  Several  such  tubes  may  be 
kept,  so  that  a  number  of  observations  can  be  made  if  necessary. 
For  thoroughly  mixing  the  blood  and  diluting  fluid,  one  or 
more  small  glass  globules  are  placed  in  the  tube.  By  using 
different  colored  glass  globules,  different  specimens  can  be 
readily  differentiated. 


24  CLINICAL  BLOOD   EXAMINATION. 

"  For  measuring  the  diluting  fluid,  pipettes  containing  1  and 
•J-  c.c.  are  used;  these  are  marked  at  995  and  990  c.mm.  and  495 
and  490  c.mm.  respectively.  With  these  graduations  the  follow- 
ing dilutions  may  be  obtained :  1 : 200,  1 : 100,  and  1 : 50,  with 
the  appropriate  capillary  pipette. 

"  Having  measured  the  diluting  fluid,  according  to  the  event- 
ual dilution  desired,  the  blood  capillary  is  filled  by  touching  the 
exuding  drop  of  blood  and  allowing  it  to  completely  fill  itself. 
The  blood  may  be  obtained  in  the  usual  manner  from  the  lobule 
of  the  ear,  the  first  drops  being  wiped  away. 

"  The  hole  in  the  nipple  allows  free  air-way  so  that  there  is  no 
hindrance  to  the  action  of  capillarity.  When  filled,  any  blood 
on  the  outside  of  the  pipette  is  rapidly  wiped  off  and  the  tube 
is  inserted  into  the  mixer  until  the  point  is  one-half  to  three- 
fourths  of  an  inch  above  the  level  of  the  contained  liquid. 

"  The  nipple  is  then  held  in  such  a  way  that  the  hole  lies 
under  the  thumb  of  the  operator.  When  this  is  the  case  it  is 
slightly  squeezed,  and  then,  while  the  pressure  is  continued,  the 
bulb  is  rotated  so  that  the  hole  is  free  again.  In  this  way  the 
blood  is  squirted  out,  but  not  sucked  back  again.  The  pro- 
cedure is  extremely  simple  and  really  requires  no  practice, 
given  an  operator  who  is  not  possessed  of  'five  thumbs.'  In 
order  to  wash  out  the  remains  of  the  blood  the  point  of  the 
capillary  is  dropped  into  the  diluting  fluid;  the  bore  instantly 
fills  itself.  It  is  then  withdrawn  and  the  pressure  and  rotation 
of  the  nipple  are  repeated.  This  has  to  be  repeated  several 
times,  and  occupies  a  few  seconds  of  time.  It  has  been  sug- 
gested that  a  certain  amount  of  error  is  introduced  by  measur- 
ing the  diluting  fluid  in  a  pipette,  the  inner  surface  of  which 
retains  some  moisture ;  this  is  extremely  small  in  amount  if  the 
pipette  is  emptied  slowly,  and  comparative  readings  with  the 
Thoma-Zeiss  apparatus  show  that  the  error  is  negligible. 

"  To  mix  the  blood  and  diluting  fluid  thoroughly,  the  mixer  is 
placed  between  the  opposed  hands,  which  are  rubbed  backward 
and  forward;  the  mixer  is  rotated  thereby,  and  the  glass 
globules  cause  a  thorough  dispersion  of  the  corpuscles  in  the 
fluid. 

"  A  drop  of  sufficient  size  is  then  placed  upon  the  counting 
chamber,  and  the  cover-slip  is  slipped  on  sideways  in  the  usual 
way  I  prefer  the  Thoma-Zeiss  counting  chamber. 


COUNTING    THE    CORPUSCLES.  25 

"  The  advantages  of  this  method  are : 

"1.  The  ease  and  thoroughness  with  which  the  pipette  can 
be  cleaned. 

"2.  The  manifest  advantage  of  the  self-measurement  of  the 
blood. 

"3.  The  avoidance  of  the  objectionable  necessity  of  using  the 
mouth  to  suck  fluids  into  the  pipette. 

"4.  The  measurement  of  the  diluent  can  be  done  carefully 
and  calmly  beforehand,  and  any  error  corrected  without  taking 
any  more  blood. 

"  5.  The  greatly  smaller  cost  of  the  pipette. 

"6.  The  same  pipette  is  useful  for  making  various  dilutions 
in  serum  diagnosis,  by  using  several  mixing  vessels  filled  before- 
hand with  dilute  fluid." 


CHAPTEE  HI. 

OLIVER'S    TINTOMETER— CENTRIFUGALIZING    THE    BLOOD- 
HAEMOGLOBIN  ESTIMATION— SPECIFIC  GRAVITY- 
STAINED   SPECIMENS— BACTERIOLOGICAL 
EXAMINATION. 

OLIVEE'S  TINTOMETER. 

KECENTLY  a  method  of  estimating  corpuscles  by  means  of 
their  optical  effect,  and  without  directly  counting  them,  has 
been  introduced  by  Dr.  Oliver.  For  practical  purposes  an 
actual  counting  of  the  corpuscles  must  be  considered  a  neces- 
sity ;  not  only  since  the  number  of  leucocytes  is  not  without  im- 
portance (e.g.,  in  the  diagnosis  of  enteric  fever),  but  also  since 
these  cells  may  be  so  abundant  that  they  may  interfere  with  the 
use  of  optical  methods,  as  in  the  case  of  leukaemia.  Neverthe- 
less the  instrument  is  very  accurate  and  useful  in  many  cases. 
Its  principle  is  based  on  the  fact  that  if  a  small  quantity  of  blood 
is  gradually  diluted  with  Hay  em's  solution1  in  a  test  tube 
whose  sides  are  flattened  so  that  its  mouth  forms  a  rectangle 
about  15  mm.  by  5  mm. ,  and  a  candle  flame  is  looked  at  through 
the  mixture,  there  is  to  be  seen,  ivlien  a  certain  degree  of  dilution 
is  readied,  a  bright  horizontal  line  on  the  glass  (see  Fig.  15). 
This  line  is  made  up  of  a  large  number  of  minute  images  of  the 
flame,  produced  by  the  longitudinal  striation  of  the  glass.  If 
the  quantity  and  quality  of  blood  used  is  in  every  instance  the 
same,  the  degree  of  opacity  depends  wholly  on  the  amount  of 
Hayem's  solution  added.  It  is  found  that  with  normal  blood 
the  amount  of  diluting  solution  necessary  to  allow  the  image  of 
the  candle  flame  to  be  seen  through  the  mixture  is  always  the 

1  Hydrargyri  perchloridi, 0. 5  gm. 

Sodii  chloridi,         .         .      •  „        .         .         .         .        .  1.0    " 

"     sulphatis,       .        .,.-•' 5.0 

Aquae  destillatae, 200.0c.c, 


OLIVER'S  TINTOMETER. 


uo 


FIG. 


same,  and  can  be  very  accurately  fixed,  so  that  a  variation  of 
one  per  cent  in  the  number  of  corpuscles  can  be  distinguished 
by  noting  the  amount  of  diluting  solution  which  must  be  added 
before  the  image  of  the  flame  appears.  To 
collect  the  blood,  Oliver  uses  a  capillary 
pipette  containing  about  10  c.mm.  (one  large 
drop),  and  used  exactly  in  the  same  way  as  the 
v.  Fleischl  capillary  pipette 
(see  Fig.  12). 

One  pipette  full  of  normal 
blood  is  gradually  diluted  in 
the  flattened  tube  with  Hay- 
is.  —  capillary  em's  solution  until  a  bright 
Diver's  horizontal  line  caused  by  the 
image  of  candle  flame  becomes 
visible  through  the  mixture.  The  point  to 
which  the  column  of  the  mixture  then  reaches 
is  marked  100,  and  then  space  between  that 
point  and  the  bottom  of  the  tube  is  divided 
into  100  equal  parts.  The  point  marked  100 
is  then  equivalent  to  5,000,000  red  corpuscles; 
90  =  4,500,000,  80  =  4,000,000,  and  so  on,  each 
degree  on  the  scale  corresponding  to  a  difference 
of  50,000  corpuscles  (Fig.  13). 

Use  of  Oliver's  Tintometer. 

The  capillary  pipette  is  filled  in  the  usual 
way,  and  the  outside  carefully  and  quickly 
wiped  if  necessary.  The  medicine  dropper 
(previously  filled  with  Hayem  solution)  is  then 
connected  with  the  polished  blunt  end  of  the 
pipette  by  means  of  the  rubber  tube  (Fig.  14), 
and  blood  washed  into  the  test  tube  as  shown 
in  Fig.  14.  If  the  previous  haemoglobin  esti-  FIG.  13.— Measuring 
mation  has  shown  ninety  to  one  hundred  per 
cent  of  coloring  matter  we  can  safely  add  the 
diluting  solution  rapidly  until  the  point  marked  80  is  reached. 
If  the  coloring  matter  is  lower  we  must  cease  our  rapid 
dilution  correspondingly  sooner.  When  we  get  near  the  point 


60 


S.O 


Tube  for  Oliver's 
Tintometer. 


CLINICAL   BLOOD    EXAMINATION. 


at  which  the  flame-image  is  likely  to  appear,  the  diluting 
fluid  must  be  added  a  few  drops  at  a  time.  After  each  ad- 
dition put  the  thumb  over  the  mouth  of  the  tube  and  turn  it 
upside  down  once  or  twice  to  mix  the  blood  thoroughly,  wiping 


FIG.  14. — Use  of  Oliver's  Tintometer.    Method  of  washing  in 
the  blood. 


FIG.  15.— Method  of 
Holding  the  Tinto- 
meter while  Diluting. 
Note  the  bright  hori- 
zontal line  in  the 
fluid,  indicating  that 
enough  diluting  fluid 
has  been  added. 


the  thumb  each  time  on  the  edge  of  the  tube  so  as  to  put  back 
what  fluid  has  adhered  to  it.  At  a  certain  point  the  image 
will  suddenly  become  visible.  It  is  seen  soonest  if  we  rotate 
the  tube  on  its  long  axis,  as  the  image  becomes  visible  earliest 
at  the  sides  of  the  tube.  The  whole  process  should  be  carried 
on  in  a  perfectly  dark  room,  and  the  diffused  light  of  the  candle 
must  be  shut  off  from  the  eye.  This  is  best  done  by  fitting  the 
tube  into  the  hand  as  shown  in  Fig.  15  with  the  long  axis  in 
line  with  candle,  holding  the  tube  close  to  the  eye,  and  standing 
about  ten  feet  from  the  candle.  In  the  use  of  both  of  his  in- 
struments Oliver  uses  only  the  small  wax  candle  known  as 
Christmas  candles,  whose  flame  is  of  the  most  convenient 
size. 


CENTRIFUGALIZING   THE   BLOOD.  29 


THE    ILEMATOCRIT. 

THE  haematocrit  of  Hedin,  though  a  comparatively  new  in- 
strument, has  undergone  considerable  modification  and  improve- 
ment in  the  last  few  years  and  as  remodelled  and  improved  by 
Judson  Daland  is  now  coming  into  use  in  this  country.  Its 
direct  and  obvious  object  is  simply  to  ascertain  the  relative 
volume  or  mass  of  the  corpuscles  and  of  the  plasma  in  a  drop  of 
blood;  but  the  hope  of  its  advocates  has  usually  been  that  it 
would  supplant  entirely  or  mostly  the  long,  tedious,  and  eye- 
destroying  process  of  counting  with  the  Thoma-Zeiss  instrument. 
Whereas  the  latter  needs  sometimes  an  hour's  hard  work  and 
eye  strain  to  make  an  accurate  count  of  red  cells,  with  Daland' s 
centrifugal  machine  one  can  get  the  result  in  five  minutes  with- 
out any  strain  on  the  eyes. 

Daland  maintains  the  superior  accuracy  of  his  instrument  in 
most  cases  as  a  further  advantage  of  its  use.  The  estimation 
of  corpuscles  depends  on  the  length  of  the  column  of  corpuscles 
packed  down  by  centrifugal  force  at  the  end  of  a  capillary  tube 
filled  with  blood  and  whirled  with  great  rapidity  in  a  horizontal 
plane.  The  more  corpuscles  the  longer  the  column. 

Wherever  there  is  much  variation  in  the  shape  or  size  of  the 
cells,  as  in  many  forms  of  anaemia,  leukaemia,  etc.,  the  hsematocrit 
is  evidently  inaccurate,  inasmuch  as  the  misshapen,  under-  or 
oversized  corpuscle  will  pack  down  differently  from  the  normal 
cells,  three  million  undersized  cells  making  a  shorter  column  in 
the  tube  than  three  million  healthy  ones.  This  is  recognized 
by  the  advocates  of  the  instrument,  which  is  accordingly  recom- 
mended only  in  those  cases  in  which  we  know  that  there  are  no- 
considerable  variations  in  the  size  or  shape  of  the  red  cells. 
These  are  usually  cases  in  which  no  very  great  anaemia  is  pres- 
ent and  in  which  consequently  the  labor  of  counting  the  large 
number  of  corpuscles  is  greatest.  It  seems,  therefore,  as  if  the 
hsematocrit  might  relieve  us  of  the  most  irksome  part  of  blood- 
counting  without  loss  of  accuracy. 

Against  this  there  is  to  be  said  that  we  do  not  as  yet 
know  how  far  the  elasticity  and  compressibility  of  otherwise 


30  CLINICAL   BLOOD   EXAMINATION. 

healthy  corpuscles  may  vary  and  how  far  such  a  variation  may 
invalidate  the  standard  of  tight  packing  established  from  other 
cases.  Further,  there  is  known  to  be  a  certain  amount  of  varia- 
tion in  the  size  and  volume  of  a  healthy  person's  corpuscles,  both 
between  nations  and  between  members  of  one  nation,  and  it  is 
yet  to  be  shown  whether  this  variation  is  sufficient  to  make  the 
result  of  the  hsematocrit  liable  to  a  greater  error  than  those  of 


FIG.  16.— Capillary  Tube  of  Heematocrit  with  Rubber  Attached. 

the  Thoma-Zeiss  instrument.  There  is  no  doubt  that  the  lat- 
ter is  a  slower,  more  tedious  instrument ;  the  question  is  still 
open  whether  or  not  it  is  the  more  accurate.  Daland  reports 
wide  variations  between  his  counts  and  those  of  his  colleague 
and  between  different  counts  by  one  observer  at  different  times, 
using  the  Thoma-Zeiss  instrument,  while  with  the  hsematocrit 
the  variations  are  but  slight. 

In  testing  these  results  I  have  made  parallel  counts  of  a  pa- 
tient's blood  with  several  of  the  house  physicians  at  the  Massa- 
chusetts General  Hospital  during  the  last  two  years  and  our 
differences  have  never  exceeded  the  limit  of  error  laid  down  by 
Eeinert — namely,  two  per  cent.  I  think  Daland  must  have 
been  unfortunate  in  his  results. 

If,  then,  the  error  of  the  Thoma-Zeiss  instrument  is,  as  I 
believe,  not  over  two  per  cent  under  ordinary  circumstances  and 
with  correct  technique,  it  does  not  seem  likely  that  the  haema- 
tocrit  is  a  more  accurate  as  well  as  a  simpler  and  quicker  in- 
strument. 

To  use  the  Daland  hsematocrit  we  prick  the  ear  as  usual  and 
with  the  help  of  a  bit  of  rubber  tube  attached  to  one  end  of  the 
capillary  tube  (Fig.16)  suck  in  enough  blood  to  fill  it  entirely. 
Usually  we  draw  in  more  than  enough  and  it  enters  the  rubber 
tube  as  well,  but  this  is  no  harm.  It  is  nearly  impossible  to  fill 
the  glass  tube  exactly  and  no  more,  inasmuch  as  the  proximal 
end  of  it  is  hidden  inside  the  rubber  tube.  The  commonest 


CENTKIFUGALIZING   THE   BLOOD. 


31 


mistake  at  this  point  is  incomplete  filling  of  the  capillary  tube, 
as  a  very  large  drop  is  needed  to  do  it. 

As  soon  as  it  is  full,  put  the  finger  (greased  with  vaseline) 


FIG.  17. — Daland's  Hsematocrit.  Two  capillary  tubes  in  place  on  the  horizontal  whirling 
beam.  The  instrument  i«  to  be  fastened  to  the  edge  of  some  solid  and  bulky  piece  of 
furniture  by  means  of  the  thumb- screw  seen  at  the  bottom  of  the  cut.  If  not  very 
tightly  secured,  it  will  work  loose  when  the  handle  is  revolved  rapidly. 


tightly  over  the  free  end  of  the  glass  tube  and  then,  but  not  till 
then,  draw  off  the  rubber  tube  and  adjust  the  glass  as  quickly 
as  possible  in  the  place  prepared  for  it  on  one  of  the  horizontal 
arms  of  the  whirling  machine  (Fig.  17).  A  similar  tube  (empty) 


32  CLINICAL   BLOOD    EXAMINATION. 

should  be  put  on  the  other  arm  of  the  crosspiece  to  make  the 
balance  true.  "We  must  be  quick  about  this,  else  the  blood  will 
coagulate.  The  handle  of  the  instrument  is  then  revolved  at 
least  seventy  times  a  minute  for  two  minutes,  at  the  end  of 
which  time  (sometimes  less)  the  column  of  blood  cells  is  packed 
so  tight  that  no  further  whirling  has  any  effect  on  its  length. 
Great  care  should  be  taken  that  the  horizontal  beam  is  securely 
attached  to  the  main  part  of  the  instrument,  as  it  is  capable 
of  doing  serious  damage  should  it  come  off  while  whirling 
nine  thousand  revolutions  a  minute,  which  is  the  rate  usually 
attained. 

It  is  well  to  put  a  little  vaseline  on  the  point  where  the  blunt 
end  of  the  tube  rests  (a,  Fig.  17)  to  prevent  any  of  the  blood 
sticking  there  when  we  come  to  take  the  tube  out  and  read  it. 

The  capillary  tube  is  marked  off  into  one  hundred  equal 
divisions  and  provided  with  a  magnifier  like  that  on  clinical 
thermometers.  Laid  on  a  piece  of  white  paper  it  is  easy  to  read 
off  the  number  of  divisions  occupied  by  the  blood  column,  al- 
though the  end  of  it  is  often  frayed  or  bevelled  in  a  way  that 
precludes  great  accuracy.  In  normal  blood  the  white  corpuscles 
hardly  show  at  all  in  the  tube.  They  accumulate  at  the  free 
end  of  the  column  of  red  cells,  but  unless  a  leucocytosis  is 
present  their  presence  is  indicated,  if  at  all,  only  by  a  slight 
grayish  blur  at  the  end  of  the  red  column  and  cannot  be  accu- 
rately measured.  This  blur  is  another  difficulty  in  the  way  of 
deciding  precisely  where  the  end  of  the  red-cell  column  is. 

To  estimate  the  number  of  red  corpuscles  from  the  length  of 
the  column,  we  call  each  degree  of  the  scale  on  the  tube  100,000 
cells,  or  a  little  more.  Thus  if  the  blood  column  in  the  tube 
ends  at  about  the  mark  50  we  consider  that  the  blood  has  rather 
more  than  5,000,000  red  corpuscles  per  cubic  millimetre.  So 
far  all  observers  agree  on  the  figures,  but  as  to  just  how  much 
more  or  less  than  100,000  each  degree  on  the  scale  is  worth  there 
is  some  variation  between  different  observers .  Daland, 1  in  a  long 
series  of  comparative  observations  of  making  blood  counts  and 
hsematocrit  estimations  on  the  same  case,  conclude  that  each 
degree  of  the  scale  on  the  capillary  tube  corresponds  to  99,390 
corpuscles. 

1  University  Med.  Mag.,  November,  1891. 


HAEMOGLOBIN   ESTIMATION.  33 

The  writer  in  a  series  of  forty  observations  on  healthy 
persons,  in  each  of  which  a  count  of  corpuscles  with  the  Thoma- 
Zeiss  instrument  and  a  volumetric  estimation  with  Daland's 
haematocrit  was  made,  found  the  value  of  one  degree  on  the  glass 
scale  to  vary  between  105,000  and  123,000  red  corpuscles,  the 
average  being  112,000. 

It  certainly  seems  a  priori  as  if  variations  in  the  specific 
gravity  of  the  corpuscles  or  in  the  properties  of  the  plasma 
might  make  a  considerable  difference  in  the  number  of  revolu- 
tions needed  to  reduce  the  column  of  corpuscles  to  its  smallest 
size. 

So  far  as  I  can  learn,  the  use  of  this  instrument  in  Europe 
has  been  chiefly  for  the  direct  information  it  affords  as  to  the 
volume  of  the  red  cells  and  the  amount  of  respiratory  surface  in 
the  blood,  rather  than  for  the  indirect  information  it  may  give 
us  as  to  the  number  of  the  red  cells.  It  does  not  seem  as  yet  to 
be  supplanting  the  Thoma-Zeiss  counter. 

Its  bulk  and  the  noise  it  makes  must  for  the  present,  I  think, 
prevent  its  extensive  use  outside  of  hospitals.  The  noise  it 
makes  is  a  very  loud  and  disagreeable  one,  and  will  deter  many 
from  using  it  in  private  practice. 

HEMOGLOBIN  ESTIMATION. 
/.    Von  FleiscliTs  Hcemoglobinometer. 

Until  recently  the  instrument  most  used  both  here  and  in 
Europe  is  that  of  v.  Fleischl.  In  France  Hay  em  rules  supreme 
in  the  matter  of  instruments,  as  in  everything  else  concerning 
the  blood,  and  in  England  Oliver's  apparatus  is  used  to  a  cer- 
tain extent.  The  v.  Fleischl  instrument  will  be  described  first. 
The  principle  of  its  use  is  that  of  directly  comparing  the  tint  of 
the  blood  with  various  parts  of  a  strip  of  colored  glass  ("  gold- 
purpur")  whose  color  shades  gradually  from  a  deep  red  at  one 
end  to  clear  glass  at  the  other.  The  glass  and  the  blood  are 
brought  before  the  eye  side  by  side  and  a  direct  color  judgment 
is  attempted. 
3 


34 


CLINICAL    BLOOD    EXAMINATION. 


Use  of  v,  FleischVs  Scemometer. 

(a)  To  use  the  instrument  fill  one  side  of  the  metallic  cell  (a, 
Fig.  19)  about  one-quarter  full  of  distilled  water  and  carry  it 
to  the  bedside,  together  with  the  little  capillary  pipette  (B,  Fig. 

18)  and  the  needle    for    puncturing.      The    capillary    pipette 
{  must  be  scrupulously  cleaned  and  dried  before 

use.  This  is  best  done  by  drawing  a  needle 
and  thread  (the  latter  wet  with  alcohol  and 
ether)  through  the  eye  of  the  capillary  tube. 
When  the  drop  of  blood  is  flowing  freely  from 
the  ear,  put  the  end  of  the  little  pipette  hori- 
zontally into  the  side  of  the  drop,  which  will 
at  once  fill  the  tube  by  capillary  attraction  if 
the  latter  is  clean  and  dry.  Carefully  but 
quickly  wipe  away  any  blood  that  may  be  on 
the  outside  of  the  pipette,  and  make  sure  that 
the  blood  in  it  is  just  flush  with  the  surface 
at  each  end  and  does  not  present  a  concave 
or  convex  surface.  Then  put  it  into  the  water 

FIG.   is.-  "A,   colored  contained  in  one  of  the  partitions  of  the  metal- 
B,  capillary  iic  cen  and  rattle  it  quickly  back  and  forth, 
so  that  the  water   may  be  forced   in  first  at 

one  end  and  then  at  the  other.     So  far  in  the  process  we  must 

work  very  quick  to  prevent  coagulation  which  in  some  cases 

takes  place  very  rapidly. 

(6)  After  this  the  cell  with  the  capillary  tube  still  immersed 

in  it  may  be  put  in  place  on  the  body  of  the  instrument  (see  Fig. 

19)  and  carried  to  a  room  or  closet  where  daylight  can  be  ex- 
cluded and  artificial  light  used  to  read  the  instrument  by.     Then 
the  expulsion  of  the  blood  from  the  capillary  tube  may  be  com- 
pleted by  forcing  a  few  drops  of  water  from  a  medicine  dropper 
through  the  capillary  pipette  and  into  the  compartment  where 
the  mixing  has  been  begun.     Using  the  metal  handle  of  the 
pipette  as  a  stirrer,  mix  very  thoroughly  the  blood  and  water 
in  every  part  of  the  compartment,   looking  after  the  corners 
especially.     Then  using  a   medicine   dropper,  fill  both   com- 
partments of  the  cell  to  the  brim  with  distilled  water,  taking 
.care  that  neither  overflows  into  the  other,  and  adjust  the  com- 


HEMOGLOBIN   ESTIMATION.  35 

partment  containing  the  clear  water  so  that  it  comes  over  the 
slip  of  colored  glass,  while  through  the  compartment  containing 
the  blood  light  thrown  upward  by  the  reflector  below  passes 
directly  to  the  eye.  Turn  the  thumb  screw  (see  Fig.  19,  T)  back 
and  forth  until  the  color  of  the  glass  is  the  same  as  that  of  the 
blood,  and  read  off  the  number  on  the  scale  which  corresponds 


FIG.  19. — v.  Fleischl's  Haemometer.  a,  Partition  into  which  blood  is  put ;  a',  partition 
into  which  water  is  put ;  (?,  mixing  cell ;  K,  K,  colored  glass  slip  (see  Fig.  11,  A)  ; 
P,  P,  metal  frame  on  which  scale  is  marked  ;  R,  S,  reflector  ;  T,  screw  which  moves 
the  frame,  P,  P. 

to  that  color.  This  gives  the  percentage  of  haemoglobin, 
100  being  the  color  of  normal  blood  for  men  and  80-90  for 
women. 

(c)  Matching  the  colors  is  not  at  all  easy  at  best,  but  may  be 
somewhat  aided  by  observing  the  following  precautions : 

1.  Do  not  stand  (or  sit)  facing  the  light,  but  sideways  (i.e.,  at 
A  or  B,  never  at  C,  Fig.  20) .  For  we  wish  to  avoid  that  the 
image  of  one  compartment  should  come  on  the  upper  half  of  the 
retina  and  of  the  other  compartment  on  the  lower  half,  inasmuch 
as  the  upper  half  of  the  retina  is  less  sensitive  to  light  than  the 
lower  and  so  a  less  accurate  judge  of  color.  By  sitting  as  in 
Fig.  13,  A  or  B,  we  get  the  compartments  whose  colors  we 
are  to  match,  on  the  right  and  left  halves  of  the  retina,  which 
are  equally  sensitive  in  most  persons. 


36 


CLINICAL  BLOOD   EXAMINATION. 


B 


2.  Use  as  little  light  as  possible,  and  always  less  light  for  a 
blood  having  a  low  haemoglobin  percentage  than  for  one  nearer 
the  normal.  Slight  color  distinctions  are  abolished  if  there  is 
any  more  light  than  is  necessary  for  simple  illumination ;  too 

much  light  dazzles  us 
slightly  and  so  makes  us 
less  sensitive  in  color  dis- 
crimination. 

3.  Roll    up    a   piece    of 
paper  (preferably  black)  into 
a  tube  of  such  size  that  it 
will    fit    over    the  metallic 
cell  (D,  Fig.  20)  and  rest  on 
the  platform  of  the  instru- 
ment.    Looking  through  this 
with  one  eye  we  can  judge 
more  accurately  than  with- 
out it.     Keep  the  other  eye 
closed. 

4.  Use  first  one  eye  and 
then    the    other,    and   never 

look  more  than  a  few  seconds  at  a  time,  as  the  eye  very  quickly 
gets  sufficiently  fatigued  to  lose  its  finer  sensibility.  Hence  the 
impression  of  a  first  glance  is  better  than  a  long  look. 

5.  Move  the  thumb  screiu  with  short,  quick  turns  rather  tJian 
slowly  and  gradually,  for  sudden  color  changes  affect  the  retina 
more  than  gradual  ones.  Suppose,  for  example,  we  have  got  as 
far  as  to  decide  that  the  tint  of  the  diluted  blood  corresponds  to 
that  of  glass  somewhere  between  the  numbers  40  and  60  on  the 
scale.  Move  the  screw  suddenly  from  40  to  55 ;  the  shock  of 
the  change  will  probably  convince  you  that  the  blood  color  is 
lighter  than  55.  Therefore  start  this  time  at  55  and  move  it 
suddenly  to,  say,  45,  which  may  show  that  45  is  too  light. 
Thus  by  a  series  of  quick  movements  of  the  screw  getting 
shorter  and  shorter  each  time  (with  frequent  rests  for  the  eyes) 
we  can  probably  get  it  down  to  a  matter  of  doubt  between,  say, 
42  and  45.  Beyond  that  few  persons  can  go  and  many  can  never 
learn  to  read  without  an  error  of  five  to  ten  per  cent. 


FIG.  20.—  L,  Light;  A  and  B,  right  positions  for 
observer  ;  C,  wrong  position  for  observer  ;  D, 
cell  in  place. 


NECESSARY   ERRORS.  37 

6.  If  the  preliminary  reading  shows  a  reading  of  thirty  per 
cent  or  less,  two  or  three  pipettes  full  of  blood  should  be  used 
and  the  reading  divided  by  2  or  3.  A  considerable  error  can 
thus  be  avoided. 

Necessary  Errors. 

So  far  as  I  can  see,  a  certain  amount  of  error  is  absolutely 
necessary,  inasmuch  as  the  bit  of  colored  glass  to  be  seen  at  any 
one  time  through  the  aperture  of  the  instrument  is  not  (like  the 
blood)  all  of  one  tint,  but  includes  a  variation  of  twenty  per  cent  in 
color,  i.e.,  if  the  glass  appearing  at  one  end  of  the  aperture  is 
opposite  50  on  the  scale,  that  seen  at  the  other  end  of  the  aper- 
ture will  either  be  at  30  or  at  70.  We  have,  therefore,  to  pick  out 
as  well  as  we  can  the  color  of  the  centre  of  the  bit  of  glass  show- 
ing through  the  cell  and  compare  the  color  at  that  point  with 
the  color  which  is  evenly  distributed  throughout  the  whole  of 
the  blood-and-water  compartment.  This  is  of  course,  strictly 
speaking,  impossible.  We  can  no  more  get  hold  of  and  sepa- 
rate out  the  color  of  that  central  point  than  we  can  seize  and  hold 
fast  the  present  moment.  It  eludes  our  grasp.  This  difficulty 
is  somewhat  lessened  by  shutting  off  from 
view  all  but  a  small  section  of  both  compart- 
ments with  a  bit  of  black  cardboard  or  metal 
in  which  a  slit  is  cut  as  in  Fig.  21.  The 
slit  is  put  at  right  angles  to  the  partition 
which  divides  the  cell  so  that  the  blood  tint 
is  seen  at  b  and  the  glass  tint  at  w. 

Many  persons    are  not  sensitive  enough 
to  colors  to  attain  any  reasonable  degree  of 
accuracy  with  the  instrument,  and  there  is 
moreover  a  very  considerable  difference  be-     FIG.  21. -shield 
tween  different  instruments  in  respect  to  the        use  with  v. 

.  Haemometer. 

color  ot  the  glass  slip. '     Finally  the  instru- 
ment has  been  shown  to  be  entirely  unreliable  for  percentages 
of  haemoglobin  under  20.     This  error,  however,  can  be  mostly 
eliminated  by  using  several  pipettes-full  of  blood  and  making 
corresponding  reduction  in  the  reading. 

All  these  difficulties  render  the  instrument  an  unsatisfactory 

1  Old  instruments  read  lower  than  those  recently  manufactured. 


38  CLINICAL   BLOOD    EXAMINATION. 

one  in  many  ways.     Its  bulk  and  expense  are  also  considerable 
drawbacks. 

II.    Oliver's  Hcemoglobiiwmeter. 

Oliver's  instrument  corrects  two  errors  which  are  inherent 
in  v.  Fleischl's. 

1.  It  has  no  sliding  scale  of  color,  but  compares  the  blood 
tint  successively  with  definite  tints  of  glass,  each  of  which  is 
even.     The  tints  are  worked  out  to  correspond  to  the  specific 
dilution  curve  of  blood,  for : 

2.  Since  every  colored  liquid  changes  color  at  a  different 
rate  when  diluted,  the  dilution  curve  of  blood  does  not  corre- 
spond to  that  of  glass  (which  behaves  in  this  respect  like  a 
liquid).      The  glass  wedge  of  v.   Fleischl's  instrument  repre- 
sents a  single  color  regularly  diluted  and  does  not  correspond 
in  its  degrees  to  the  colors  of  blood  diluted  at  a  similar  rate. 
The  scale  of  Dr.  Oliver's  instrument  is  measured  to  correspond 
to  the  actual  colors  of  the  blood's  dilution  curve,  by  means  of 
the  tintometer. 

In  other  respects  the  principle  of  the  instrument  is  like 
v.  Fleischl's,  and  the  method  of  using  the  two  is  practically  the 
same  except  that  in  Oliver's  reflected  light  is  used  instead  of 
transmitted  light.  Oliver's  instrument  consists  of  a  series  of 
twelve  tinted  glass  discs  corresponding  to  the  haemoglobin  per- 
centages from  10  to  120  and  arranged  in  two  rows  (see  Fig.  22a) . 
The  intermediate  degrees  are  measured  by  means  of  "  riders"  of 
colored  glass,  which  can  be  laid  on  top  of  the  primary  color 
discs  so  as  to  deepen  the  tint  seen. 

The  capillary  pipette  (Fig.  22  b)  is  somewhat  stouter  than  v. 
Fleischl's,  but  is  used  in  the  same  way  to  collect  the  blood, 
which  is  then  forced  out  of  it  with  water  from  a  medicine  drop- 
per (which  is  fitted  with  a  rubber  tube  to  slip  over  the  blunt  end 
of  the  pipette)  (Fig.  22  c)  and  washed  into  a  mixing  cell  (Fig. 
22  d)  similar  to  v.  Fleischl's,  except  for  the  absence  of  a  central 
partition.  Here  the  blood  is  mixed  in  the  usual  way  with  water 
and  the  cell  filled  to  the  brim  and  covered  with  a  small  glass 
plate.  The  blood  thus  prepared  is  brought  close  to  the  scale 
and  there  compared  with  the  tint  of  the  different  standard  color 
discs.  If  it  matches  one  of  them  the  observation  is  complete ; 


OLIVER'S  H^EMOGLOBINOMETER. 


39 


if  not  we  use  one  of  the  glass  riders  which  enables  us  to  read 
within  two  and  a  half  degrees.  A  fuller  set  of  riders  can  be 
obtained  so  as  to  make  it  possible  to  .read  down  to  1  per  cent. 

The   standard   is    usually   arranged    for    candle-light,    but 
another  set  of  discs  can  be  obtained  adjusted  to  daylight  read- 


FIG.  22.—  Oliver's  Haemoglohinometer.    a,  Standard  color  disks ;  b,  capillary  pipette; 
o,  \vashingtube;  d,  mixing  cell. 


ings.  The  latter  are  less  accurate.  The  same  precautions  as  to 
the  exclusion  of  outer  light  by  means  of  a  "  hydroscope"  tube, 
resting  the  eye  frequently,  etc.,  must  be  observed  with  this 
instrument  as  with  v.  Fleischl's.  [It  can  be  obtained  of  J.  H. 


40  CLINICAL   BLOOD   EXAMINATION. 

Smith  &  Cie.,  Zurich  (Wollishofen),  for  115  francs  plus  duties 
and  expressage,  or  of  the  Tintometer  Company,  6  Farringdon 
Avenue,  London,  E.  C.]  The  candle  should  be  placed  three  or 
four  inches  from  the  instrument  and  arranged  to  light  both  the 
blood  and  the  color  discs  alike. 

A  word  as  to  the  use  of  the  riders.  The  instrument  as  used 
for  clinical  work  usually  has  two  riders:  the  one  having  the 
deeper  tint  is  used  on  the  upper  half  of  the  scale,  the  other  on 
the  lower.  Suppose  we  have  decided  that  the  blood  color  is 
between  60  and  70.  Put  the  rider  on  the  60  disc  and  compare 
again.  If  the  blood  is  darker  than  the  60  disc  plus  the  rider 
the  percentage  is  approximately  67|  (since  it  is  higher  than 
60+5  [the  rider]  and  lower  than  70).  If  it  just  matches  the 
60  plus  its  rider,  the  reading  is  65.  If  the  blood  is  paler  than 
this,  yet  darker  than  60,  it  is  about  62^.  An  error  of  about  2  de- 
grees is  obviously  inevitable. 

ESTIMATING  THE  SPECIFIC  GRAVITY  OF  THE  BLOOD. 

The  simplest  and  most  available  method  for  clinical  use  is 
that  of  Hammerschlag, l  a  modification  of  Roy's2  method. 
Chloroform  is  heavier  than  blood;  benzol  is  lighter.  Mix  in  a 
urinometer  glass  such  quantities  of  the  two  that  the  specific 
gravity  taken  by  an  ordinary  urinometer  is  about  1059,  i.e.,  that 
of  normal  blood.  Puncture  the  ear,  draw  a  drop  of  blood  into 
the  tube  of  a  Thoina-Zeiss  pipette,  'a  small  medicine  dropper,  or 
any  other  capillary  tube,  and  blow  it  out  again  into  the  chloro- 
form-benzol mixture.  The  blood  does  not  mix  at  all  with  these 
liquids  but  floats  like  a  red  bead.  If  it  sinks  to  the  bottom  add 
chloroform,  if  it  rises  to  the  top  add  benzol,  until  finally  the 
drop  remains  stationary  in  the  body  of  the  liquid,  showing  that 
its  specific  gravity  is  just  that  of  the  surrounding  mixture. 
Then  take  the  specific  gravity  of  the  liquid,  as  we  do  of  urine, 
and  you  have  the  specific  gravity  of  the  drop  that  floated  in  it. 
The  following  precautions  are  needed : 

1.  Have  the  inside  of  the  urinometer  glass  perfectly  dry  and 
clean ;  otherwise  the  drop  of  blood  may  cling  to  it  and  flatten 
out  against  it. 

1Wien.  klin.  Wochenschrift,  iii.,  1,018,  1890. 
2  Proceedings  of  Physiological  Society,  1884. 


SPECIFIC    GRAVITY.  41 

2.  It  is  usually  well  to  have  more  than  one  drop  of  blood  in 
the  glass  in  case  any  mishap  occurs  with  the  first  one. 

3.  Add  the  chloroform  and  benzol  a  few  drops  at  a  time,  and 
after  each  addition  stir  the  whole  mixture  thoroughly  with  a 
glass  rod. 

4.  If  we  have  reason  to  suppose  the  blood  will  be  lighter 
than  normal  (i.e.,  if  the  haemoglobin  is  probably  low,  vide  supra), 
it  saves  time  to  start  with  a  lighter  mixture  of  chloroform  and 
benzol. 

5.  Avoid  having  any  air  within  the  blood  drop.     This  can 
generally  be  seen  either  in  the  capillary  tube  or  after  the  drop 
is  in  the  mixture.     It  is  safer  to  take  the  middle  portion  of  the 
blood  drawn  into  the  capillary  tube,  as  both  the  first  and  the 
last  portions  of  the  column  are  more  apt  to  have  air  in  them. 

6.  The  whole  process  should  be  done  as  quickly  as  possible, 
else  the  chloroform  or  benzol  may  work  into  the  blood  drop  and 
affect  its  weight. 

It  is  better  to  have  a  urinoineter  with  a  scale  running  as  high 
as  1070,  but  this  is  not  essential,  for  the  clinically  important 
specific  gravities  are  low,  not  high. 

The  importance  of  the  specific  gravity  of  the  blood,  as  hinted 
above,  is  not  so  much  for  itself,  but  because  it  runs  parallel  to 
the  percentage  of  haemoglobin  and  gives  a  figure  from  which  the 
latter  can  be  computed. 

The  specific  gravity  of  the  blood  plasma  varies  very  little 
(except  in  dropsy  from  any  cause) ,  and  in  the  corpuscles  them- 
selves the  variable  element  is  the  haemoglobin.1  Consequently 
in  most  non-dropsical  patients  the  specific  gravity  of  the  whole 
blood  varies  directly  as  the  haemoglobin.  The  following  excep- 
tions to  this  rule  must  be  borne  in  mind. 

1.  In  leukaemia  the  specific  gravity  is  relatively  higher  than 
the  haemoglobin  on  account  of  the  weight  of  the  leucocytes. 

2.  In  pernicious  anaemia  with  high  color  index  (see  below) 
the  haemoglobin  is  about  two  per  cent  higher  than  we  should 
gauge  it  to  be  judging  by  the  specific  gravity. 

Now,  as  it  is  far  easier  to  take  the  specific  gravity  accurately 
than  to  use  the  v.  Fleischl  haemometer,  and  as  the  instruments 
needed  are  already  in  the  possession  of  most  physicians  and 

1  Except  in  dropsy  in  which  the  corpuscles  themselves  may  get  water- 
soaked. 


42 


CLINICAL   BLOOD    EXAMINATION. 


the  solutions  not  expensive,  there  are  evidently  great  advantages 
in  taking  the  haemoglobin  in  this  indirect  way.  The  chloroform- 
benzol  mixture  can  be  filtered  and  then  used  over  again  indefi- 
nitely, and  the  bulk  and  weight  of  the  urinometer  with  its  glass 
and  the  chloroform  and  benzol  bottles,  are  far  less  than  that  of 
the  hsemoglobinometer. 

In  dropsical  cases  we  must  still  use  the  hsemoglobinom- 
eter.  In  other  conditions  I  do  not  see  why  it  should  not  be 
supplanted  by  the  cheaper,  easier,  more  accurate,  and  equally 
quick  method  of  calculating  by  specific  gravity.  To  do  this 
one  of  the  following  tables  may  be  used.  (I.  is  from  Harnmer- 
schlag,  using  the  method  above  described ;  II.  is  modified  from 
Schmaltz,  "Pathologie  des  Blutes,"  etc.,  Leipsic,  1896,  using  a 
direct  weighing  method.)  Apparently  a  degree  of  specific  grav- 
ity means  much  more  at  the  top  of  the  scale  (i.e.,  6.6  per  cent) 
than  at  the  bottom  (If  per  cent).  These  tables  are  of  course  not 
accurate,  and  further  research  will  be  needed  to  make  them  so. 


Spec.  Grav. 
1033-1035 
1035-1038 
1038-1040 
1040-1045 
1045-1048 
1048-1050 
1050-1053 
1053-1055 
1055-1057 
1057-1060 


Haemoglobin. 
=  25-30  per  cent. 
=  30-35 
=  35-40 
=  40-45 
=  45-55 
=  55-65 
=  65-70        u 
=  70-75 
=  75-85 
=  85-95 


II. 

Spec.  Grav.  Haemoglobin. 

1030     =  20  per  cent.  ± 

1035     =  30 

1038     =  35 

1041     =  40 

1042.5=  45 

1045.5=  50 

1048  =  55 

1049  =  60 

1051  =  65 

1052  =  70 
1053.5=  75 
1056  =  80 
1057.5  =  90 
1059  =  100 


STUDY  or  THE  FINER  STRUCTURES  OF  THE  BLOOD. 

The  study  of  dried  and  stained  specimens  with  the  help  of 
the  aniline  dyes  gives  us  much  of  interest  and  importance  in 
regard  to  the  blood.  More  can  be  told  about  a  given  case  by 
the  study  of  a  dried  and  stained  cover-glass  specimen  than  by 
any  other  single  method. 

Preparation  of  Cover-Glass  Specimens. 

(a)  Covers  carefully  cleaned  with  soap  and  water  are  ar- 
ranged at  the  bedside  in  such  position  that  we  can  quickly  pick 


STUDY   OF   THE    FINER   STRUCTURES    OF   THE    BLOOD.        43 

them  up  without  touching  their  surfaces  (see  Fig.  I).1  The  ear 
is  punctured  in  the  usual  way,  and  one  of  the  cover-glasses 
touched  to  the  summit  of  the  drop  as  soon  as  it  emerges.  This 
cover-glass  is  then  let  fall  upon  another 
in  such  a  way  that  their  corners  do  not 
coincide  (Fig.  23).  If  the  covers  are 
clean  the  drop  spreads  at  once  over  their 
whole  surface ;  as  soon  as  it  stops  spread- 
ing, slide  off  the  top  one  witJiout  lifting 
them  apart,  but  exactly  in  the  plane  of 
their  surfaces.  Have  a  gas  or  alcohol 
flame  at  hand  and  dry  instantly  if  you 
want  to  get  the  very  best  specimens; 
but  this  is  not  at  all  necessary  for  most  clinical  purposes. 
The  under  cover-glass  is  always  better  spread  than  the  upper. 

(6)  These  covers  have  now  to  be  fixed  either  by  heat  or  by 
half  an  hour's  immersion  in  absolute  alcohol  and  ether  (equal 
parts),  or  by  the  same  mixture  (30  c.c.  each)  plus  five  drops 
of  a  saturated  alcoholic  solution  of  corrosive  sublimate  (five 
minutes'  immersion),  or  by  exposure  to  the  vapor  of  forty -five 
per  cent  formaldehyde.  I  'have  used  all  these  methods,  but 
found  none  of  them  to  compare  favorably  with  the  method  of 
heat  fixation  when  we  wish  to  study  the  leucocytes  or  the  nuclei 
of  any  cell. 

When  we  wish  to  see  chiefly  the  changes  in  the  red  cells  (as 
in  studying  the  malarial  organism,  nucleated  red  corpuscles, 
degenerative  changes,  etc.),  the  alcohol  and  ether  method  is 
good.  But  when,  as  in  the  majority  of  cases,  it  is  the  white 
cells  in  which  our  interest  centres,  the  use  of  heat  is  very  greatly 
to  be  preferred.  Heat  serves  not  simply  to  fix  the  cells  on  the 
glass  and  to  prevent  degenerative  changes,  but  also  to  modify 
and  greatly  improve  the  staining  power  of  the  cell  when  Ehr- 
lich's  triacid  stain  is  used. 

The  method  of  fixation  by  alcohol  and  ether  needs  little 
comment,  the  cover-glasses  being  simply  left  in  the  mixture 
half  an  hour  or  as  much  longer  as  is  convenient.  Half  an  hour 

1 1  often  poise  them  on  corks  so  that  their  corners  are  readily  accessible 
to  the  fingers.  The  process  of  making  blood  films  is  far  easier  if  another 
person  prepares  the  drop  for  us  so  that  we  can  stand  ready  with  a  cover- 
glass  in  each  hand  to  catch  the  drop  as  soon  as  it  emerges. 


44  CLINICAL   BLOOD   EXAMINATION. 

is  enough.  In  most  cases  we  use  dry  heat.  The  best  way  to 
do  this  is  in  a  dry -heat  sterilizer  at  a  temperature  of  140°- 
155°  C.,  according  to  the  stain  used.  The  temperature  must  be 
watched  very  closely,  and  as  soon  as  it  reaches  the  desired 
point  the  heat  should  be  removed.  Gradual  heating  and 
gradual  cooling  are  best.  If  we  cannot  easily  get  access  to  such 
an  instrument,  we  can  manage  very  well  with  any  small  iron  or 
copper  box  having  a  door  or  lid  and  a  hole  for  a  cork  which  is 
perforated  for  the  thermometer  bulb.  This  supported  over  a 
gas  or  alcohol  flame  does  very  well.  It  needs  about  ten  minutes 
to  get  the  temperature  to  150°  C.,  and  as  soon  as  it  gets  there  the 
specimens  should  be  taken  out.  The  same  end  can  be  accom- 
plished somewhat  less  accurately  with  a  strip  of  copper  sup- 
ported over  a  Bunsen  burner  or  a  small  gas  or  oil  stove.  The 
copper  plate  should  be  about  a  foot  long  and  two  or  three  inches 
wide.  Such  a  plate  supported  on  an  iron  tripod  over  a  flame 
gets,  after  a  few  minutes,  to  have  a  fixed  temperature  at  any 
given  distance  from  the  flame,  the  heat  passing  off  at  the  end  of 
the  plate  as  fast  as  it  comes,  and  so  not  accumulating.  On  this 
plate  find  the  boiling  point  of  water  by  dropping  small  drops 
of  water  on  it,  and  put  the  cover-glasses  at  this  point  face,  down- 
ward. They  may  be  left  there  for  from  fifteen  minutes  to  as  long 
.as  you  please;  but  with  the  stain  which  I  have  used,  fifteen 
minutes'  heating  gives  as  good  results  as  a  longer  period,  and 
excellent  specimens  can  often  be  made  with  five  minutes'  heat- 
ing.1 After  allowing  the  specimens  to  cool  they  are  ready 
for  staining. 

Staining. 

For  all  details  of  structure  the  Ehrlich  tricolor  mixture  or 
one  of  the  numerous  modifications  of  it  is  most  convenient. 

1  With  a  little  practice  one  can  learn  to  make  excellent  specimens  by 
simply  passing  the  cover-glass  through  a  Bunsen  or  alcohol  flame  about 
twenty  times  very  rapidly.  The  rate  of  speed  must  be  learned  by  experi- 
ment, i.e.,  such  a  speed  and  such  a  number  of  exposures  to  the  flame  as 
turns  out  to  give  on  staining  a  bright  yellow  color  to  the  red  corpuscles 
(never  red  or  brown  or  gray),  a  good  definition  to  the  blue-stained  nuclei 
and  to  the  violet  or  pink  granules  of  the  polynuclear  leucocytes.  These 
are  the  essentials  of  a  well-stained  specimen,  and  they  depend  (a)  on  the 
heating,  (6)  on  the  make  of  stain,  but  only  slightly  on  the  length  of  stain- 
ing (vide  infra). 


STAINING.  45 

The   most  useful  and  easily   obtained   of  these   is   made   by 
mixing : 

Saturated  watery  solution  of  orange  G,       .         .         .         .  6  c.c. 

"    acid  fuchsin,         .         .         .          4  c.c. 

To  these  add  a  few  drops  at  a  time,  shaking  between  each  ad- 
dition : 

Saturated  watery  solution  of  methyl  green,        .         .         .  6.6  c.c. 

Then  add: 

Glycerin, 5  c.c. 

Absolute  alcohol,  .         .         .         .  .         .         .         10   " 

Water,  .        .- '.        .        .         15  " 

Shake   well  for   one  to  two   minutes.     Let  stand  twenty-four 
hours.     Do  not  filter. 1     G.  G  rubier 's  colors  are  best. 

I  have  used  only  this  stain  for  the  past  two  years,  and  have 
never  seen  any  other  which  compares  with  it  in  brilliancy  and 
general  usefulness. 

The  staining  process  is  remarkably  simple.  A  drop  of  the 
stain  is  simply  spread  over  the  surface  of  the  cover-glass  speci- 
men with  a  glass  rod  and  washed  off  again  with  water  after  two 
or  three  minutes  or  as  much  longer  as  is  convenient.  With  this 
mixture  it  is  impossible  to  overstain.  If  the  specimen  look  too 
dark  (brown  or  red  instead  of  orange-yellow)  it  is  not  because 
of  overstaining,  but  because  of  underlieating .  It  needs  a  good 
deal  of  heat  to  bring  out  the  full  brilliancy  of  the  three  colors, 
and  the  100°-120°  C.  usually  recommended  for  heating  is  entirely 
insufficient  with  this  stain  unless  continued  for  a  long  time. 

If  overheated  the  specimen  looks  pale  lemon  yellow  to  the 
naked  eye,  and  under  the  microscope  everything  is  blurred  and 
dim. 

I  am  convinced  that  any  one  who  has  once  seen  how  much 
is  brought  out  by  a  good  make  of  triple  stain  will  never  use  any 
other  for  clinical  purposes.  Eosin  (one-per-cent  alcoholic  solu- 
tion) followed  after  a  few  minutes  by  Delafield's  hsematoxylon 
for  one  minute,  or  methyl  blue  one-half  minute,  gives  a  very 

1  An  absolutely  reliable  triple  stain  from  Ehrlich's  latest  formula  can 
be  had  of  Walter  Dodd,  apothecary  to  the  Massachusetts  General  Hospital 
A  65-cent  bottle  will  stain  several  thousand  specimens. 


46  CLINICAL   BLOOD    EXAMINATION. 

striking  contrast  stain,  but  does  not  bring  out  the  points  most 
essential  in  clinical  blood  work.  To  "control"  Ehrlich's  triple 
stain  with  eosin-haematoxylon  or  eosin-methyl  blue  is  like  con- 
trolling a  chronometer  with  a  fifty-cent  clock.  The  latter  stains 
are  very  valuable  for  the  study  of  the  finer  structure  of  nuclei, 
for  karyokinetic  figures  and  basophilic  granules,  but  not  for 
diagnosis. 

After  staining  and  washing  in  water,  the  covers  are  dried 
between  layers  of  filter  paper  and  mounted  in  Canada  balsam, 
ready  for  examination  with  the  one-twelfth  oil-immersion  lens, 
with  wide-open  diaphragm. ' 

Differential  Counting. 

The  only  procedure  in  the  microscopic  examination  of  such 
specimens  which  needs  any  description  is  that  of  making  the 
so-called  "differential  count"  of  the  leucocytes  (i.e.,  determining 
what  percentage  of  the  leucocytes  present  belongs  to  each  of 
the  sub-varieties  as  described  on  pp.  62-67).  To  do  this  accur- 
ately we  should  examine  at  least  five  hundred  leucocytes — the 
examination  being  simply  the  classification  of  them  under  their 
different  sub-varieties.  A  movable  stage  is  very  convenient 
though  not  essential  for  this  purpose.  With  such  a  stage  the 
technique  is  simply  to  start  with  the  lens  in,  say,  the  upper  left- 
hand  corner  of  the  blood  film  and,  by  turning  the  screw  of  the 
mechanical  stage,  move  the  preparation  slowly  past  the  eye 
until  the  upper  right-hand  corner  is  reached.  During  this 
process  as  the  cells  appear  in  the  field  they  are  checked  off  and 
put  down  under  one  or  another  heading.  Then  move  the  stage 
so  that  the  lens  is  just  one  field's  diameter  nearer  the  right-hand 
lower  corner  of  the  preparation,  and  go  back  again  from  right 
to  left,  following  the  serpentine  track  indicated  above  in  Fig. 
7.  To  move  the  lens  just  one  field's  diameter  we  have  only  to 
fix  the  eye  on  a  cell  at  the  extreme  edge  of  the  field,  and  then 
move  the  stage  till  that  cell  disappears  out  of  sight  on  the  oppo- 

1  Of  late  I  have  used  dry  lenses  a  great  deal — the  7  or  even  the  5  of  Leitz 
— on  account  of  their  larger  field.  Most  cells  can  he  easily  recognized 
with  this  power  after  we  have  well  learned  their  looks  by  earlier  study  of 
specimens  with  the  immersion  lens.  If  in  doubt  about  any  cell,  it  is  easy 
to  pull  out  the  tube  of  the  microscope  or  put  on  the  immersion  lens. 


DIFFERENTIAL   COUNTING.  47 

site  side  of  the  field.  Thus  we  avoid  any  chance  of  counting  the 
same  cells  twice,  and  yet  are  sure  not  to  miss  seeing  any. 

As  we  go  back  and  forth  in  this  way,  we  notice  chiefly  the 
white  cells  of  course,  but  yet  keep  our  eyes  open  for  any  unusual 
appearances  in  the  red  cells.  Usually  these  move  by  in  a 
monotonous  stream,  one  looking  much  like  another,  but  in 
pathological  blood  we  must  always  be  on  the  lookout  for  nu- 
cleated red  cells,  degenerative  changes,  and  variations  in  size 
and  shape.  In  malarial  cases  of  course  our  scrutiny  is  directed 
chiefly  upon  the  red  cells. 

If  we  have  not  the  help  of  a  movable  stage  we  try  to  do  the 
same  thing  moving  the  slide  with  the  fingers.  With  moderate 
care  there  is  no  danger  of  counting  the  same  cells  twice,  but 
we  cannot  help  missing  a  good  many  altogether,  so  that  although 
accurate  the  process  takes  longer. 

When  leucocytosis  is  present,  at  least  one  thousand  leuco- 
cytes can  be  found  in  a  single  well-spread  seven-eighth-inch  cover- 
glass  specimen.  In  normal  blood  we  may  need  to  go  through 
two  to  three  covers. 

BACTERIOLOGICAL  EXAMINATION. 

Blood  obtained  by  the  ordinary  method  of  puncture  is  not 
fit  for  bacteriological  examination.1  The  following  is  the  better 
way: 

Sterilize  the  skin  over  the  flexor  surface  of  the  bend  of  the 
elbow,  and  wash  off  thoroughly  the  agents  used  for  sterilization 
with  boiled  water  or  boiled  normal  salt  solution.  Have  an  as- 
sistant grasp  the  upper  arm  so  as  to  prevent  the  venous  return 
and  distend  the  large  veins  at  the  elbow.  Into  the  most  promi- 
nent of  these  plunge  a  sterilized  hollow  needle  connected  with 
the  bulb  of  a  sterilized  syringe.  All  traces  of  antiseptics  must 
be  carefully  washed  out  of  the  needle  and  the  syringe  bulb  be- 
fore using. 

When  the  needle  penetrates  the  wall  of  the  vein  the  blood 
usually  begins  to  flow  into  the  bulb  of  the  syringe,  and  this  is 
hastened  by  gently  withdrawing  the  piston  until  1-2  c.c.  of  blood 
are  in  the  bulb.  Then  withdraw  the  needle,  press  a  pad  of 
sterilized  gauze  over  the  wound,  and  expel  the  blood  before  it 

1  See  Kiihnau's  comparative  experiments  in  Deut.  med.  Woch.,  1897, 
No.  25. 


48  CLINICAL   BLOOD   EXAMINATION. 

coagulates  into  a  blood-serum  culture  tube  so  that  it  shall  run 
down  over  the  whole  surface  of  the  "  slant"  and  collect  a  little  at 
the  bottom.  The  tubes  are  then  put  at  once  into  the  thermostat. 

In  examining  for  the  gonococcus  the  blood  is  to  be  mixed 
with  equal  parts  of  agar-agar  (previously  melted  down  so  as  to 
be  mixable  but  not  hot  enough  to  kill  the  organisms) ,  and  then 
plated. 

The  farther  examination  of  cultures  falls  outside  the  scope  of 
this  book. 

In  the  above  procedure  the  only  difficulties  are:  1.  Some- 
times it  is  hard  to  find  a  vein  and  to  get  the  needle  into  it. 
2.  Occasionally  we  get  the  needle  entirely  through  the  vessel 
into  the  tisuses  on  the  other  side. 

If  the  blood  does  not  flow  readily  into  the  bulb  one  of  these 
two  mistakes  is  usually  the  cause,  but  occasionally  in  those 
whose  vessels  are  very  small  or  whose  circulation  is  very  feeble 
(as  in  the  moribund)  it  is  very  hard  to  get  the  requisite  amount 
of  blood.  Only  practice  helps  us  to  avoid  these  difficulties. 

The  procedure  causes  hardly  more  pain  than  the  use  of  an 
ordinary  subcutaneous  injection ;  the  process  of  sterilization  is 
usually  more  irksome  to  the  patient  than  the  puncture. 

Bleeding  is  trifling,  and  within  twenty-four  hours  there  is 
usually  no  trace  of  the  puncture  left.  A  sterilized  dressing  with 
moderate  pressure  should  be  applied. 

OTHER  METHODS  or  BLOOD  EXAMINATION. 

It  is  perhaps  worth  while  briefly  to  mention  some  other 
methods  of  blood  examination  of  which  no  account  will  be 
given. 

1.  Determination  of  the  alkalinity  of  the  blood.     No  accur- 
ate and  clinically  available  method  has  yet  been  devised.     De- 
spite the  interesting  work  of  Kraus,   Caro,  Lowy,  Biernacki, 
v.  Limbeck,  and  others,  *I  am  still  unable  to  get  hold  of  any 
clinically  valuable  information  given  by  the  determination  of 
alkalinity. 

2.  Resistance  of  the  red  corpuscles   to  the  influence  of  dis- 
tilled water.     As  is  well  known,  water  breaks  up  red  cells,  but 
if  we  add  a  certain  amount  of  alkali,  say  NaCl,  the  cells  re- 
main uninjured.     The  amount  of  NaCl  which  has  to  be  added 


OTHER   METHODS.  49 

to  prevent  the  destruction  of  red  cells  is  from  0.44  to  0.48  per 
cent.  Under  certain  pathological  conditions  it  needs  either 
more  or  less  of  the  salt  to  keep  the  cells  intact,  i.e.,  they  pos- 
sess an  increased  or  diminished  power  of  resistance  against  the 
destroying  influences  of  distilled  water.  The  degree  of  con- 
centration necessary  to  maintain  red  corpuscles  intact  is  known 
as  the  isotonic  coefficient  of  the  blood  as  stated  in  terms  of  a 
given  salt;  0.44-0.48  is  thus  the  coefficient  of  normal  blood  cor- 
puscles in  NaCl. 

Possibly  this  method  of  examining  blood  may  in  the  future 
give  us  knowledge  of  clinical  value.  At  present  it  is  not  clini- 
cally applicable. 

The  resistance  of  the  blood  cells  to  the  influence  of  elec- 
tricity, heat,  and  mechanical  pressure  has  also  been  investigated 
in  various  conditions  of  health  and  disease. 

3.  The  rapidity  of  coagulation  varies  markedly  in  different 
diseases,  but  no  reliable  way  of  measuring  it  has  yet  been  found. 

4.  The  amount  of  solids  in  a  given  quantity  of  blood  can  be 
determined  by  weighing  a  given  amount  of  blood  before  and 
after  six  hours'  drying  at  65°  C.     Inasmuch  as  the  haemoglobin 
percentage  and  the  specific  gravity  run  practically  parallel  with 
the  amount  of  solids  this  method  has  no  considerable  clinical 
value. 

4 


PART   II. 

PHYSIOLOGY    OF    THE    BLOOD. 


CHAPTER  IV. 

ONLY  such  portions  of  our  knowledge  of  blood  physiology 
will  be  entered  upon  here  as  are  necessary  for  an  understanding 
of  the  small  group  of  pathological  changes  which  can  be  profit- 
ably investigated  by  clinicians.  This  limits  us  for  the  present 
to  the  morphology  of  the  blood,  its  coloring  matter,  and  its  density 
under  physiological  conditions. 

APPEAEANCE  OF  FBESH  NORMAL  BLOOD. 

A  drop  of  normal  blood  spread  between  slide  and  cover-glass 
as  directed  on  page  7  and  examined  immediately  with  a  one- 
twelfth  immersion  lens,  amazes  us  first  of  all  by  the  entire  ab- 
sence of  any  red  color.  All  we  see  is  a  colorless  liquid  in  which 
masses  of  very  pale  greenish-yellow  discs  are  floating  or  lying. 

.    I.  Red  Corpuscles. 

(a)  If  the  blood  is  spread  thickly  the  blood  discs  are  often 
arranged  in  the  form  of  rouleaux  (Fig.  24).  The  entire  absence 
of  this  tendency  to  rouleaux  formation  is  pathological.  It  is  to 
be  avoided,  of  course,  as  far  as  possible,  as  it  gives  us  only  the 
thin  edges  of  the  corpuscles  to  look  at  and  covers  up  much  that 
we  need  to  study.  Thin  spreading  of  the  blood  is  therefore  im- 
portant. 

(6)  There  is  not  much  variation  from  the  accurately  round 
shape  of  each  corpuscle  in  normal  blood,  except  where  one  is 
indented  by  another.  As  they  are  moved  about  by  the  currents 
set  in  motion  by  the  gradual  drying  up  of  the  plasma  and  strike 
against  each  other,  they  bend,  double  up,  or  indent  each  other, 


PHYSIOLOGY   OF  THE  BLOOD.  51 

like  bags  of  jelly,  but  yet  always  have  a  strong  tendency  to 
return  elastically  to  their  round  outline  when  free  from  pres- 
sure. Thus  a  corpuscle  passing  through  a  narrow  passage  be- 
tween two  leucocytes  will  be  flattened  out  like  a  worm ;  but  as 
soon  as  it  emerges  on  the  other  side,  it. will  be  as  round  as 
before. 

(c)  The  central  biconcavity  of  the  cell,  being  thinner  than  the 
rim,  is  lighter  colored.    Just  how  much  lighter  should  be  learned 
by  practice  so  that  we  may  detect  any  abnormal  pallor  of  the 
corpuscles  due  to  lack  of  haemoglobin.     Pallor  is  to  be  seen 
mostly  in  the  centre  of  the  cell,  which  in  extreme  cases  seems 
almost  transparent.      This  is  not  to  be   confounded  with  the 
highly  refractile,  glistening-white  centres    seen  as  a  mark  of 
necrosis  as  soon  as  the  blood  begins  to  dry  up.     A  fuller  de- 
scription of  these  appearances  is  given  in  the  chapter  on  the 
malarial  organisms,  with  some  forms  of  which  they  may  be 
confounded. 

(d)  Slight  variations  in  size  are  present  among  normal  red 
discs,  and  here  again  only  practice  can  teach  us  where  the  normal 
limits  end  and  the  pathological  begin.      Cells  may  be  (patho- 
logically) all  undersized  or  all  oversized,  so  that  a  standard  of 
comparison  is  not  always  to  be  looked  for  in  the  preparation 
itself. 

(e)  If  we  focus  carefully  on  a  single  red  cell  we  can  usually 
make  out  a  fine,  wavy,  so-called  molecular  motion  in  it.     This  is 
quite  different  from  the  active  amoeboid  movements  observed 
in  dying  cells,  and  from  the  rapid  dancing  of  malarial  pig- 
ment. 

(/)  The  familiar  appearance  of  spines  all  over  the  cells 
usually  called  "  crenation"  need  not  be  described  here  (see  Fig. 
27,  p.  86). 

But  it  is  the  very  earliest  beginnings  of  crenation  that  lead 
to  mistakes,  as  when  only  one  projection  has  been  developed 
and  that  points  toward  the  eye,  so  that  a  bright  spot  in  the  cor- 
puscles is  all  we  see. 

( g)  Unless  we  disinfect  the  skin  before  puncturing  we  must 
be  prepared  to  find  in  fresh  preparations  (a)  oil  drops1  (b)  epi- 
thelium; (c)  particles  of  "dirt;"  (d)  small  colorless  motile 

!In  some  conditions  the  blood  really  contains  fat.  (Vide  infra,  "Li- 
paemia.") 


52  CLINICAL   BLOOD    EXAMINATION. 

organisms  about  1  n  in  diameter,  which  are  not  at  all  rare  but 
whose  nature  is  unknown  to  me. l 

(h)  We  may  make  a  rough  estimate  of  the  number  of  red  cells 
present  if  we  take  care  to  spread  the  drop  of  the  same  thickness 
each  time.  The  eye  gets  used  to  the  ordinary  look  of  a  well- 
filled  field  of  corpuscles  and  notices  a  look  of  thinness  if  any 
considerable  anaemia  is  present. 

(i)  The  degenerative  changes  to  be  seen  in  normal  blood  after 
long  exposure  to  the  air,  which  can  get  in  between  slide  and 
cover,  are  described  in  detail  later  on.  In  pathological  blood 
we  may  find  these  as  soon  as  the  blood  is  drawn. 

//.    White  Cells. 

(a)  The  white  or  colorless  corpuscles  are  but  little  different 
from  the  red  in  color,  the  latter  being  so  nearly  colorless.     We 
first  notice  them  either  by  their  amoeboid  movements,  or  because 
they  are  not  moved  by  the  plasma  currents,  but  stand  like  a  rock 
round  the  sides  of  which  the  current  of   red  cells  is  broken. 
They  are  slightly  larger  in  most  instances  than  the  red  cells ;  but 
this  difference  shows  less  in  the  fresh  specimens  where  the  leu- 
cocyte keeps  its  spherical  shape  than  in  the  dried  and  stained 
preparations,   where  it  is  usually   somewhat  flattened.     Their 
shape  is  very  irregular  and  their  edges  often  look  tattered. 

In  some  leucocytes  the  amoeboid  motions  are  entirely  absent. 
These  are  the  smallest  cells,  and  in  them  a  single  nucleus  filling 
most  of  the  cell  can  often  be  seen.  They  are  much  more  nearly 
spherical  and  less  irregular  than  the  amoeboid  cells. 

The  large  amoeboid  leucocytes  are  more  or  less  granular,  and 
in  certain  lights  these  granules  look  quite  dark  and  are  some- 
times mistaken  for  bits  of  malarial  pigment.  This  is  especially 
true  of  the  coarse  granular  cells  seen  occasionally;  staining 
shows  these  large  granules  much  more  distinctly  ( =  eosino- 
phile — see  below,  p.  65) ;  cells  of  this  type  are  the  most  actively 
amoeboid  of  all. 

(b)  The  most  important  point  in  connection  with  the  leu- 
cocytes is  their  ratio  to  the  red  cells.     This  is  estimated  in 
fresh  specimens  not  by  any  actual  counting  but  by  reference  to 
a  standard  fixed  in  the  mind  by  study  of  normal  specimens,  and 

1  Since  this  was  written  the  same  appearances   have  been  carefully 
studied  by  Mtiller  and  Stokes  (see  page  59) . 


PHYSIOLOGY    OF   THE   BLOOD.  53 

any  considerable  increase  of  the  white  cells  would  be  noticed  at 
once.  Naturally  we  must  not  judge  from  any  one  part  of  the 
slide,  as  the  distribution  of  the  leucocytes  may  be  unequal  in 
different  parts  of  it. 

///.  Blood  Plates.1 

Unless  the  number  of  these  elements  is  increased  by  some 
pathological  influence,  we  seldom  notice  them  at  all  in  normal 
blood.  This  may  be  because  we  do  not  work  quickly  enough  in 
preparing  our  specimen.  Hayem  recommends  that  the  cover- 
glass  be  laid  upon  the  slide  before  the  puncture  is  made ;  as  soon 
as  the  drop  emerges  it  is  allowed  to  run  in  between  slide  and 
cover  by  capillary  attraction,  thus  avoiding  contact  with  the  air.a 
The  blood  plates  are  irregularly  shaped,  very  cohesive  elements, 
about  one-half  the  diameter  of  a  blood  disc,  usually  seen  cling- 
ing together  in  masses  like  zooglcea.  They  are  colorless  and 
not  amoeboid  and  look  like  debris. 

IV.  Fibrin  Network. 

After  a  specimen  of  fresh  blood  has  stood  for  some  time  ex- 
posed to  as  much  air  as  can  creep  in  between  slide  and  cover- 
glass,  we  begin  to  notice  a  network  of  fine  straight  lines  in  the 
spaces  between  the  corpuscles.  Here  and  there  these  filaments 
seem  to  radiate  from  a  centre  where  irregular,  colorless  masses, 
apparently  blood  plates,  are  to  be  seen  (Fig.  24). 

No  stain  is  needed  to  demonstrate  these  fibrin  threads,  but 
a  small-aperture  diaphragm  and  very  little  light  makes  them 
plainer.  Their  only  importance  is  that  under  certain  pathologi- 

1  It  is  probable  that  the  elements  included  under  this  heading  comprise 
several  different  things.     It  is  beyond  the  plan  of  this  book  to  discuss 
their  origin  and  significance,  since  they  possess  at  present  no  clinical 
value. 

2  This  is  a  very  satisfactory  way  if  we  wish  to  see  the  corpuscles  as 
fresh  and  unspoiled  as  we  can.    Put  a  cover-glass  on  a  slide  so  that  the  edge 
of  one  corresponds  with  the  edge  of  the  other,  and,  holding  them  in  this 
position  with  finger  and  thumb,  put  their  superimposed  edges  into  the  side 
of  the  drop  as  it  emerges.     It  will  run  in  between  them  by  capillary  at- 
traction.    The  blood  plates  can  be  stained  with  eosin,  and  in  the  eosin- 
haematoxylon    stain  are  easily  seen  and  their  number    approximately 
estimated. 


54 


CLINICAL   EXAMINATION   OF   THE    BLOOD. 


cal  conditions  the  fibrin  network  is  very  much  increased  and 
helps  us  in  the  diagnosis  (Fig.  25) .     Hence  it  is  of  importance 


FIG.  24.— Rouleau  Formation  and  Fibrin  Network  of  Normal  Blood. 

to  be  familiar  with  the  ordinary  closeness  of  the  network  in  nor- 
mal blood  as  a  standard  of  comparison. 


FIG.  35.— Increased  Thickness  of  Fibrin  Network. 

For  an  account  of  the  conditions  of  its  increase  see  Chapter 
IX.,  page  124. 


PHYSIOLOGY   OF   THE   BLOOD.  55 


AVERAGE  DIAMETER  OF  RED  CELLS. 

The  blood  under  normal  conditions  shows  considerable  varia- 
tions in  the  size  of  its  corpuscles  in  the  fresh  state  as  well  as  in 
stained  specimens.  * 

The  following  table  (v.  Limbeck)  shows  the  results  of  various 
observers. 

Normal  Limits.  Average  Diameter. 

Welcker diameter  =  4. 5-9. 5  //.  7  p, 

Valentin In 

Malinin 7.7  ft 

Hayem diameter  =  6-S.8//..  7.5^ 

Mallassez 7.6  fi 

Laache diameter  =  6-9  v 8. 5  n 

Bizzozero 7. 075  n 

Gram  . ,  . . diameter  =  6. 7-9. 3  /*  7. 850  n 


Average  =  1.5  n 

These  differences  depend  partly  on  differences  in  the  method 
of  measuring   (wet  or  dry),  and  partly  on  the  fact  that  the  age 

1  A  method  of  measuring,  approximately  accurate,  and  easily  appli- 
cable in  clinical  work  is  the  following  : 

Using  a  camera  lucida,  trace  on  paper  the  divisions  of  a  fine  stage  mi- 
crometer as  seen  under  a  one-twelfth  oil  immersion  lens  ;  such  micrometres 
are  usually  ruled  to  one  one-hundreth  of  a  millimetre.  Approximate  ac- 
curacy in  our  tracing  can  be  obtained  if  the  process  is  repeated  till  the 
divisions  marked  in  successive  drawings  correspond  accurately  one  with 
another.  Care  must  be  taken  that  the  paper  is  flat  upon  the  table  beside 
the  microscope,  and.  not  raised  on  a  block  or  otherwise  ;  also  that  the  part 
of  the  paper  on  which  we  draw  should  be  perpendicularly  under  the  centre 
of  the  mirror  and  not  off  to  one  side.  When  a  drawing  has  been  made 
with  these  precautions,  we  have  only  to  divide  the  space  between  each  of 
the  lines  in  our  drawing  into  ten  equal  parts,  and  we  have  a  scale,  each 
division  of  which  represents  1  //  as  seen  under  a  one-twelfth  oil-immersion 
lens,  with  the  length  of  tube  of  the  particular  microscope  used.  To  use 
our  //-scale  we  have  only  to  draw  with  the  camera  lucida  any  cell  whose 
size  we  want  to  know,  using  always  the  same  microscope,  the  same  length 
of  tube,  and  the  same  lenses,  and  having  the  drawing  paper  (as  before) 
flat  on  the  table  and  perpendicularly  under  the  mirror.  The  drawing  thus 
made  is  measured  with  the  //-scale  like  any  other  object. 

With  this  method  a  cell  can  be  measured  in  a  few  seconds  and  with 
sufficient  accuracy  (i.e.,  within  0. 5  //). 


5G  CLINICAL   BLOOD    EXAMINATION. 

and  conditions  of  nutrition  in  the  persons  selected  make  a 
difference.  In  the  new-born,  and  to  some  extent  throughout 
childhood,  the  normal  limits  of  variation  are  wider  than  in  adults 
(3.3-10.5  />-,  Hay  em) .  Sex  appears  to  have  no  constant  influence. 

Gram  '  noted  that  the  measurements  published  by  observers 
living  in  southern  Europe  are  smaller  than  those  of  northern 
Europe  (Italians  7-7.5,  Germans  7.8,  Norwegians  8.5). 

The  majority  of  any  individual's  red  cells  are  certainly  about 
7.5  I*  in  diameter,  and  this  may  accordingly  be  taken  as  our  stand- 
ard (Hay em  counts  twelve  per  cent  under  6.6  /*,  twelve  per  cent 
over  8  /*,  the  rest  7.5  />-)• 

NORMAL  NUMBER  OF  THE  RED  CELLS. 

1.  At  the  level  of  the  sea  and  in  adult  life  the  normal  number 
of  red  cells  per  cubic  millimetre  is  about  5,000,000  for  men  and 
4,500,000  for  women.     This  is  not  infrequently  increased  in  very 
vigorous,  healthy  persons ;  6,000,000  is  by  no  means  rare  among 
healthy  young  men,  and  higher  figures  are  seen  occasionally. 
Thus  Hewes 2  in  fifty  young  medical  students  found  an  average 
of  5,809,000  per  cubic    millimetre;    of  these  fifteen   exceeded 
6,000,000,  the  highest  being  6,400,000,  while  the  lowest  of  the 
whole  series  was  5,120,000.     Altitude  above  the  sea  level  raises 
the  count  invariably  (see  page  79). 

2.  The  influence  of  menstruation,  childbirth,  and  lactation  is  to 
diminish  the  red  cells  temporarily,  the  amount  of  the  diminution 
depending  not  only  on  the  amount  of  blood  lost  but  on  the 
capacity  of  the  individual   organism  for  blood  regeneration. 
At  puberty,  when   sexual  functions  are  being  established,  we 
expect    lower    counts    than    after    the    establishment   of    the 
function.     Normal  pregnancy  does  not  affect  the  count  of  red 
cells. 

3.  The  count  of  red  cells  per  cubic  millimetre  is  raised  by 
any  cause  inducing  concentration  of  the  blood,  such  as  profuse 
sweating,  and  is  lowered  by  the  temporary  dilution  of  the  blood 
after  large  draughts  of  liquid.     In  these  changes,  which  are  al- 
ways very  transient,  the  haemoglobin   and  specific  gravity  in 
a  given  drop  are  of  course  increased  with  the  corpuscles. 

1  Fortschritte  der  Medicin,  1884. 

8  Transactions  of  the  Boston  Society  of  Medical  Science,  May  18,  1897. 


PHYSIOLOGY   OF   THE   BLOOD.  57 

Vasomotar  influences  affecting  the  calibre  of  the  peripheral 
vessels  (hot  or  cold  baths,  exercise,  etc.)  may  temporarily  con- 
centrate or  dilute  the  blood  by  affecting  the  interchange  of  fluid 
between  the  vessels  and  the  surrounding  lymph  spaces.  By 
these  processes  the  blood  in  the  peripheral  vessels  may  show  an 
increase  or  diminution  in  the  cellular  elements,  the  haemoglobin 
and  specific  gravity  corresponding  to  the  greater  or  less  concen- 
tration of  the  blood  at  that  point  (on  these  points  see  below 
page  76). 

Hayem  noted  that  in  young  people  especially  the  number  of 
red  cells  varied  considerably  without  any  notable  change  in  con- 
ditions. 

4.  Influence  of  Nutrition  on  the  Number  of  Bed  Cells. 

A.  After  a  meal,  especially  when  considerable  liquid  is  taken, 
the  blood  is  temporarily  diluted  and  hence  the  count  of  red  cells 
per  cubic    millimetre  is   diminished    (v.    Limbeck;    Reinert). 
This  is  illustrated  by  the  following  case  from  v.  Limbeck. 

ADULT,  MALE,  HEALTHY. 

Red  Cells.  White  Cells.                 Hb 

11 :15  A.M 5, 530, 000  7, 660    98  per  cent. 

12  M.  dinner. 

12:15P.M 5,320,000  6,166 

1:15  "  5,480,000  8,500 

2:15  "  4,733,000  12,000 

3  :15  "  4, 872, 000  14, 000    89  per  cent. 

4:15  "  4,720,000  10,830    89 

As  the  white  cells  rise  (digestive  leucocytosis,  see  below,  page 
83)  the  red  fall. 

Fasting,  by  concentrating  the  blood,  temporarily  increases 
the  number  of  red  cells  (400,000-500,000  increase  after  twenty- 
four  hours'  fast). 

B.  General  Nutrition. — Lean,  muscular  people  have  on  the 
average  more  red  cells  per  cubic  millimetre  than  fat  people 
(Leichtenstern,    quoted  by   v.    Limbeck),    other   things   being 
equal. * 

As  above  said,  fasting  (by  concentrating  the  blood)  raises  the 
number  of  red  blood  cells,  so  that  it  is  not  simply  hunger  that 

1  The  influence  of  stasis  in  the  obese,  whose  fat  loads  the  surface  of  the 
heart,  is  to  cause  an  apparent  increase  of  red  cells  (see  below,  p.  75). 


58  CLINICAL   BLOOD    EXAMINATION. 

gives  us  the  diminution  in  red  cells  commonly  found  in  poorly 
nourished  people,  but  rather  the  influence  of  bad  hygiene  in  the 
slums,  etc. 

5.  Seasons  and  the  time  of  day  seem  to  have  no  influence  in 
themselves.     The  same  is  true  of  race  and  climate.     The  only 
exception  to  this  is  reported  in  the  work  of  E.  Below,1  who 
found  in  yellow  fever  districts  an  average  count  of  only  4,700,000 
red  cells  per  cubic  millimetre  and  the  diameter  of  the  individual 
cell  reduced  to  5.9  /*  on  the  average  (7.5  /*  =  normal). 

6.  Fatigue.—  Hayem  noted  a  loss  of  from  500,000  to  1,000,- 
000  red  cells  per  cubic  millimetre  in  the  blood  of  a  number 
of  farmers  after  •  a  hard  summer's  work,  the  counts  made  in 
September  having  been  compared  with  those  of  April  and  al- 
ways found  to  be  lower.     Whether  fatigue  is  the  only  cause  of 
this  diminution  may  be  doubted. 

7.  Age. — In  the  new-born  the  number  of  red  cells  is  very 
high  for  a  few  days  (7,000,000  to  8,800,000),  but  falls  at  the  end 
of  seven  to  ten  days  (see  page  86) . 

In  the  very  old  a  certain  degree  of  anaemia  is,  so  to  speak, 
physiological;  but  this,  which  like  the  plethora  of  the  new- 
born is  to  be  referred  not  to  the  fact  of  age,  but  to  concomitant 
influences,  is  by  no  means  invariable.  Schmaltz  reports 
6,766,000  red  cells  in  a  man  of  eighty-one  and  4,816,000  in  a 
woman  of  seventy -four. 

NOBMAL  NUMBER  OF  WHITE  CELLS. 

The  figure  usually  given  for  adults  is  7,500  per  cubic  milli- 
metre. This  varies  a  good  deal,  according  to  the  nutrition  of 
the  individual  (see  page  81)  and  also  at  different  times  of 
the  day,  owing  to  influences  not  explained.  The  influence  of 
digestion  will  be  mentioned  later.  In  animals  a  slight  shock2 
is  sufficient  materially  to  affect  the  count  of  leucocytes;  5,000 
to  10,000  may  be  called  the  normal  limits.  Eomberg  finds 
9,058  as  the  average  count  in  fifty -five  healthy  young  women. 
There  is,  I  believe,  no  evidence  to  show  whether  or  not  mental 
disturbances  (fear,  rage,  emotion  of  various  kinds)  affect  their 

1  "Deut.  Tropenhygiene,"  Berlin,  1895.     O.  Coblanz. 
2L6witt:  "Studien  z.  Physiol.  und  Pathol.  d.  Blutes,"  etc.,  Jena,  1892. 
Fischer. 


PHYSIOLOGY    OF   THE    BLOOD.  59 

number,  but  my  impression  is  that  they  do.     Other  causes  of 
variation  will  be  discussed  under  Leucocytosis. 


BLOOD  PLATES. 

The  number  of  blood  plates  is  from  400,000  to  700,000  under 
normal  conditions.  They  are  the  chief  constituents  of  white 
thrombi,  and  wherever  they  are  diminished  (e.g.t,  in  haemo- 
philia, purpura)  clotting  is  apt  to  be  slow.  They  are  increased 
in  leukaemia  and  in  many  cases  of  grave  anaemia.  In  the  severer 
types  of  many  infectious  diseases  (typhus,  erysipelas,  malaria) 
they  are  diminished,  and  in  malaria  they  are  sometimes  wholly 
absent  during  the  fever.  In  pneumonia  and  tuberculosis  they 
are  normal  or  increased.  In  purpura  and  haemophilia  they  are 
sometimes  much  diminished  or  absent. 

The  physiological  limits  of  the  amount  of  hcemoglobin  and  of 
the  specific  gravity  have  already  been  mentioned.  Under  phys- 
iological conditions  their  variations  follow  those  of  the  count 
of  red  cells. 

MULLER'S  "BLOOD  DUST." 

Miiller  1  has  recently  described  under  the  title  of  "  Haemo- 
conien,"  or  blood  dust,  a  constituent  of  normal  and  pathological 
blood  not  hitherto  noticed.  This  consists  of  small  round  color- 
less granules  about  the  size  of  the  finest  fat  drops — or  about 
i-1/*  in  diameter,  their  size  being  very  variable.  They  are 
highly  refractile  and  have  rapid  dancing  (molecular)  motion, 
but  no  power  of  locomotion.  They  are  insoluble  in  alcohol  and 
ether,  not  stained  by  osmic  acid,  and  take  no  part  in  the  forma- 
tion of  fibrin.  Stokes  and  Wegefarth,2  who  have  confirmed 
Miiller's  observations,  note  that  the  "  blood  dust"  can  be  seen 
much  more  clearly  by  the  light  of  a  Welsbach  gas  burner  than 
by  daylight.  The  latter  observers  present  a  body  of  evidence 
tending  strongly  to  show  that  these  bodies  are  the  extruded 
granules  of  neutrophilic  and  eosinophilic  leucocytes.  Granules 
apparently  identical  with  them  can  be  stained  in  fresh  speci- 
mens with  eosin  or  Ehrlich's  triacid  stain  in  a  way  apparently 

'Centralbl.  fur  allg.  Path.,  etc.,  viii.,  1896. 

2  Johns  Hopkins  Hospital  Bulletin,  December,  1897. 


60  CLINICAL   BLOOD   EXAMINATION. 

like  that  of  the  intracellular  granules. !     They  are  also  to  be  seen 
in  pus  and  in  hydrocele  fluid. 

I  have  frequently  noticed  these  granules  in  studying  fresh 
blood,  but  hitherto  supposed  them  to  come  from  the  patient's 
skin  (see  page  52,  footnote).  No  special  diagnostic  or  prog- 
nostic significance  has  yet  been  attached  to  them,  though  the 
work  of  Kanthack  and  Stokes  renders  them  of  great  interest 
with  reference  to  the  problem  of  immunity.  They  remind  one 
somewhat  of  the  description  given  by  Kahane  of  the  supposed 
organism  of  cancer. 

1Nicholls:  Phil.  Med.  Jour.,  Feb.  26,  1898. 


Examination  of  the  Blood. 


PLATE  I. 


Fig.  i.  Varieties  of  Leucocytes. 


Polymorphonuclear          ^  &«2  H\ 


L-Myelocytes 


Small  Lymphocytes 


--Large  Lymphocytes 


Eosinophile 


M|*..      Eosinophilic 
"Myelocyte 


The  Malaria!  Organism. 


N 


J      -;;v/5 
6   C'$: 


ijf 

v:.v-     M^ 


sr. 


,* 


Fig.  2. 


Fig.  3. 


B.  C.  <  'ahf.t  fee. 


I.itli.  AIIHI   v.  !•;.  A.  Fank4,  L.ipzig. 


PLATE  I. 

FIG.  1.— (a)  Polymorphonuclear  Neutrophiles.  Note  the  varieties  in 
size  and  shape  of  granules,  the  irregular  staining  of  the  nuclei,  the  light 
space  around  them,  their  relatively  central  position  in  the  cell. 

(&)  Myelocytes.  Note  identity  of  granules  with  those  just  described ; 
the  even,  pale  stain  of  nuclei ;  their  position  near  the  surface  (edge)  of  the 
cell.  The  two  cells  figured  indicate  the  usual  variations  in  the  size  of  the 
whole  cell. 

(c)  Small  Lymphocytes.     In  the  cell  at  the  left  note  transparent  proto- 
plasm ;  in  the  cell  next  to  it  note  very  pale  pink  ring  of  protoplasm  around 
nucleus  which  is  deeply  stained,  especially  at  the  periphery.     The  next 
cell  has  an  indented  nucleus  ;  its  protoplasm  relatively  distinct.     The  cell 
on  the  extreme  right  shows  no  protoplasm  and  is  probably  necrotic.     In  all 
note  absence  of  granules  with  this  stain.     With  basic  stains  blue  granules 
appear  in  the  protoplasm. 

(d)  Large  Lymphocytes.     Note  pale-stained  nuclei  and  protoplasm,  ir- 
regularity of  outline  ;  indented  nucleus  in  one.     Every  intermediate  stage 
between  these  and  the  "small"  lymphocytes  occurs,  and  the  distinction 
between  them  is  arbitrary. 

(e)  Eosinophile.     Note  irregular  shape,  loose  connection  of  granules, 
their  copper  color,  their  uniform  and  relatively  large  size,  and  spherical 
shape. 

(/)  Eosinophilic  Myelocyte.  Note  similarity  to  (6)  ordinary  my elocytes 
except  as  regards  granules.  Color  of  granules  may  be  as  in  (e)  ordinary 
eosinophile. 

All  the  above  were  stained  with  the  Ehrlich  triacid  stain,  and  drawn" 
with  camera  lucida.     Oil-immersion  objective  one-twelfth  and  ocular  No. 
iii.  (Leitz). 

FIG<  2. — Malarial  Parasites  in  Fresh  (Unstained)  Blood  (Tertian 
Forms) .  N,  JV,  normal  red  corpuscles  ;  1,  red  cell  containing  hyaline  body ; 
2,  3,  4,  5,  successive  stages  in  the  development  of  the  parasite,  showing 
acquisition  of  pigment;  6,  7,  full-grown  parasites,  the  corpuscle  no 
longer  visible  ;  8,  beginning  of  segmentation  ;  9,  segmentation.  In  6  and 
7  note  brownish  blur  behind  the  pigment  dots.  Drawn  as  in  Fig.  1. 

FIG.  3.— Tertian  Parasite  Stained  with  Eosin  and  Methyl  Blue.  The 
remains  of  the  corpuscle  containing  the  parasite  stain  pink,  the  parasite 
blue,  and  its  pigment  black.  The  stages  of  growth  correspond  with  the 
numbers  attached.  Note  in  Figs.  1,  2,  3,  and  4  the  shape  of  the  parasite, 
shown  better  than  in  fresh  specimen. 

[Owing  to  a  mistake  the  cells  in  Fig.  3  are  not  drawn  according  to  a 
single  scale  and  their  relative  sizes  must  be  disregarded.] 


CHAPTEE  V. 
FINER  STRUCTURE  OF  THE  BLOOD. 

I.  APPEARANCES  or  DRIED  AND  STAINED  SPECIMENS. 

COVER-GLASS  specimens  prepared  and  stained  as  above  di- 
rected give  us  more  information  of  interest  and  importance  than 
can  be  obtained  from  any  other  one  method  of  blood  examination. 
Approximate  ideas  of  the  quantity  of  red  cells,  of  white  cells, 
and  of  haemoglobin  can  be  formed,  parasites  and  bacteria  can  be 
seen,  and  the  whole  mass  of  evidence  based  on  the  finer  structure 
of  the  leucocytes  can  only  be  obtained  in  this  way.  The  ap- 
pearances of  a  specimen  of  normal  blood  prepared  in  this  way 
are  as  follows : 

RED  CELLS. 

1.  The  haemoglobin  stains  with  the  orange  G  of  the  tricolor 
mixture,  and  in  a  properly  heated  specimen  the  red  cells  are  of  a 
brilliant  yellow  or  pale  orange  tint.  If  overheated  they  have  a 
feebly  stained,  washed-out  look,  while  if  underheated  they  are 
more  or  less  broivn  or  gray.1 

The  degree  of  pallor  of  the  centres  corresponding  to  the 
amount  of  haemoglobin  in  the  corpuscle  can  be  gauged  much 
more  accurately  with  this  stain  than  in  the  fresh  preparations. 
The  color  of  the  edges  is  not  much  affected  by  pathological 
changes,  the  centres  being  the  test.  But  in  cases  with  extreme 
poverty  of  haemoglobin  the  colored  rim  may  be  reduced  to  a 
mere  shell  and  the  rest  may  be  almost  completely  colorless. 
The  power  to  estimate  the  amount  of  coloring  matter  in  this 
way  can  be  easily  acquired. 

An  approximate  idea  of  the  number  of  red  cells  may  be 
formed  by  any  observer  who  has  learned  to  use  a  uniform 
technique  in  each  case  and  to  spread  the  blood  of  a  standard 
thickness. 

1  This  is  a  fruitful  source  of  error.  Many  suppose  that  because  their 
specimens  come  out  too  dark  they  must  be  "burnt,"  and  so  heat  less.  In. 
fact  the  dark  tint  means  that  the  specimen  is  not  heated  enough. 


62  CLINICAL   BLOOD    EXAMINATION. 

2.  Nothing  is  seen  of  the  fibrin  or  blood  plates  as  a  rule.     In 
normal  cases   the  plasma   does  not  stain  at  all.      A  certain 
amount  of  debris  is  often  present,  usually  pink  stained. 

WHITE  COKPUSCLES. 

3.  The  chief  purpose  and  use  of  the  "  triple  stain"  is  for  dis- 
tinguishing the  varieties  of  white  corpuscles,  and  the  pathologi- 
cal states  of  the  red.     About  the  normal  red  cells  it  gives  us  no 
information  that  cannot  be  obtained  as  well  by  various  other 
stains,  but  our  knowledge  of  normal  leucocytes  has  been  im- 
mensely enlarged  by  its  use. 

In  normal  blood  stained  as  above  directed,  we  recognize  the 
following  varieties  of  white  cells : 

(1)  Small  lymphocytes  or  "  small  hyaline  forms"  (Kanthack) 
(see  Plate  I.).     These  consist  mostly  of  a  round  blue  nucleus 
about  the  size  of  a  red  cell,  and  surrounded  by  a  thin  coating  of 
protoplasm,  faintly  stained  or  invisible  (with  Ehrlich's  triple 
stain). 

The  nucleus  may  be  considerably  smaller  than  a  red  cell, 
and  may  or  may  not  be  deeply  stained.  In  my  experience  it 
is  usually  pale-stained,  but  slight  differences  in  technique  will 
greatly  affect  its  staining  power.  The  larger  it  is  the  more  apt 
it  is  to  be  pale  (see  Plate  I. ) . 

(2)  There  is  no  line  to  be  drawn  between  this  form  and  that 
now  to  be  described,  namely,  the  "  large  lymphocyte"  or  "  large 
mononuclear  cell,"  which  is  simply  larger  and  paler. 

The  small  lymphocyte  is  the  form  most  frequently  seen  in 
the  lymph  channels  and  in  chyle  and  at  the  periphery  of  the 
follicles  of  adenoid  tissue.  Whether  it  grows  in  the  circulating 
blood  into  any  other  form  of  leucocyte  is  uncertain.  In  the 
so-called  "large  lymphocyte"  the  nucleus  occupies  relatively 
less  of  the  cell  than  in  the  small  lymphocyte. 

In  many  cases  we  do  not  see  in  the  blood  any  intermediate 
forms.  Lymphocytes  are  either  "small"  (5-10  /*  in  diameter) 
or  "large"  (13-15  ;>-  in  diameter)  (see  Plate  I.). 

In  other  cases  we  find  every  intermediate  size,  both  of 
nucleus  and  of  the  cells  as  a  whole,  and  in  such  cases  it  is 
absurd  to  attempt  a  division  into  "large"  or  "small,"  though 
we  may  be  able  to  say  in  a  general  way  which  size  predominates. 


FINER   STRUCTURE   OF   THE   BLOOD.  63 

The  theory  that  the  "  large"  mononuclear  cells  or  "  large  hya- 
line forms"  (Kanthack)  come  from  the  spleen  and  the  small 
mononuclear  from  the  lymph  glands  has  been  abandoned  on  all 
sides  of  late  years. 

The  protoplasm  of  all  lymphocytes,  as  has  been  said,  is 
always  hard  to  stain  with  Ehrlich's  triple  stain.  Sometimes  it 
has  a  faint  pinkish  tinge,  more  frequently  it  is  grayish  or  very 
light  blue,  and  in  some  cases  it  .stands  out  brilliantly  trans- 
parent and  colorless  against  the  faint  purplish  tinge  of  the  sur- 
rounding plasma  (see  Plate  I.).  Although  non-granular  with 
the  triple  stain  many  of  the  lymphocytes  show  basophilic 
granules  at  the  periphery  of  their  protoplasm  when  stained  with 
eosin  and  methylene  blue.  When  thus  stained  a  ring  of  un- 
stained protoplasm  appears  around  the  nucleus.  Sometimes 
the  protoplasm  stains  diffusely  blue  with  basic  stains  and  no 
granules  can  be  made  out. 

I  have  described  the  lymphocytes  so  far  as  "mononuclear," 
but  it  is  not  rare  to  find  even  very  small  ones  (6  /*  in  diameter) 
whose  nucleus  has  a  deep  cut  in  one  side  or  has  divided  into 
two  parts.  I  believe  it  is  commoner  to  find  a  divided  nucleus 
in  the  small  forms  than  in  the  "  large  lymphocytes."  The  inap- 
plicability of  the  term  "small  mononuclear  cells"  or  "large 
mononuclear  cells"  to  this  variety  of  corpuscle  is  evident.  The 
distinguishing  mark  is  not  the  single  nucleus  but  the  absence  of 
granules,  with  Ehrlich's  stain.  (See  also  below  under  "Mast 
cells.") 

In  the  smaller  forms  of  lymphocytes  the  nucleus,  even  when 
dividing,  is  compact  and  fills  most  of  the  cell.  But  in  the  large 
forms,  instead  of  simply  being  larger  and  paler,  the  nucleus 
may  begin  to  bend  and  branch  in  the  cell,  and  then  we  get  the 
so-called 

(3)  "  Transitional  forms"  (Ehrlich),  which  are  no  bigger  than 
the  larger  size  of  -lymphocytes,  from  which  they  differ  only  in 
that  they  have  an  indentation  in  their  nucleus — either  a  narrow 
cut  or  a  bay  so  wide  that  a  "  horseshoe"  nucleus  results.  This 
is  the  transitional  form  according  to  this  nomenclature.  There 
is  no  reason  for  calling  it  so,  as  all  the  forms  of  leucocytes  are 
transitional,  but  there  is  some  convenience  in  the  name.  Like 
most  large  lymphocytes  it  is  pale  all  through — pale  in  both 
nucleus  and  protoplasm — and  often  escapes  notice  in  hasty  ex- 


64  CLINICAL   BLOOD    EXAMINATION. 

animations.  Sometimes  its  protoplasm  is  sparsely  covered  with 
faint  neutrophilic  granules. 

(4)  The  cells  usually  known  as  "  polynuclear"  are  more 
properly  called  polymorplionuclear  neutrophiles.  These  cells 
constitute  the  vast  majority  of  those  found  in  ordinary  pus. 
The  main  difference  between  them  and  those  last  described  is 
in  the  possession  of  granules,  best  seen  when  stained  by  Ehr- 
lich's  methods.  The  nucleus  stains  usually  quite  deep  blue  or 
greenish-blue,  and  irregularly,  i.e.,  more  intensely  in  some  parts 
than  in  others.  It  is  very  irregular  in  shape,  being  twisted 
about  in  the  body  of  the  cell.  Here  and  there  it  may  dive  down 
so  deeply  beneath  the  surface  of  the  cell  that  it  is  hidden  under 
a  thick  layer  of  granules,  reappearing  in  another  part  of  the  cell 
so  that  it  seems  to  be  broken  in  two.  Occasionally,  no  doubt, 
this  is  actually  the  case,  but  generally  there  are  "  underground 
connections"  between  the  apparently  separate  pieces  of  nucleus. 
Now  and  then  we  see  a  cell  (degenerating)  where  the  granules 
have  fallen  away,  leaving  the  nucleus  like  a  short,  thick  snake, 
very  rarely  two,  or  like  several  sausages  joined  by  strings. 

One  never  sees  any  two  of  these  cells  whose  nuclei  are  of  the 
same  shape.  Hence  the  term  "polyrnorphonuclear."  The 
windings  and  twistings  of  the  nucleus  have  suggested  compari- 
sons to  the  letters  Z,  S,  E,  etc. 

The  granules  which  fill  the  body  of  the  cell  and  in  which  the 
nucleus  is  embedded  stain  well  only  with  triple  stains  like  Ehr- 
lich's.  Acid  stains  like  eosin,  and  basic  stains  like  methylene 
blue,  do  not  bring  them  out  clearly.  Hence  the  term  "neutro- 
philic," which  is  not  strictly  accurate;  more  properly  they  are 
faintly  oxyphilic  J  and  can  be  faintly  stained  with  eosin.  [Hence 
Kanthack  and  other  English  observers  have  called  them  "  fine 
granular  oxyphiles,"  while  the  term  "coarse  granular  oxy- 
philes"  is  applied  to  the  cells  generally  known  as  eosinophiles. 
These  terms  are  in  some  respects  more  accurats  than  Ehrlich's, 
but  are  even  more  cumbrous  than  his.]  With  Ehrlich's  triacid 
mixture  the  granules  stain  violet  or  purple,  sometimes  pink. 
They  are  very  small  and  irregular  in  shape  and  size,  contrast- 
ing with,  the  large,  round,  "  eosinophile"  granules  (see  below). 
The  cells  being  spherical  the  granules  lie  over  and  around  the 
nucleus,  not  simply  at  the  side  of  it.  In  their  interstices  we 

1  Ehrlich's  stain  is  really  a  differential  acid  stain  and  not  neutral. 


FINER   STRUCTURE   OF   THE   BLOOD.  65 

sometimes  seem  to  see  a  pinkish  background  of  cell  substance, 
but  this  is  probably  composed  of  granules  somewhat  out  of 
focus.     In  normal  blood  these  "  neutrophilic"  granules,  which 
are  so  small  that  except   with  very  high 
powers    they   look    like   a  diffuse    stain,     ^--. 
rarely  if  ever  occur  except  in  cells  whose     • 
nucleus   has   reached    the    polymorphous 
stage.     Occasionally  we  seem  to  see  mono- 
nuclear  neutrophiles,  having  a  round  nucleus 
with    neutrophilic    granules,    but    careful 
focussing  usually  shows  that  the  appear- 
ance of  a  round  or  rod-shaped  nucleus  is 
given  by  the  tight  coiling  of  the  ribbon- 
like  nucleus  round  one  of  its  ends,  or  else  FlG-  26- 
that  a  horseshoe  nucleus  is  seen  from  the 

point  of  view  indicated  in  Fig.  26.  Thus  if  the  eye  be  at  the 
point  A  the  nucleus  will  appear  of  the  shape  indicated  in  B 
(Fig.  26). 

(5)  The  eosinophile  or  "  coarse  granular  oxyphile"  cell  has,  like 
its  predecessor,  a  polymorphous  nucleus  and  granules ;  but  the 
nucleus  is  paler  and  more  loosely  connected  to  the  granules,  and 
the  latter  are  spherical  or  oval,  of  uniform  size,  and  much  larger 
than  any  seen  in  the  neutrophilic  cell.  They  have  strong  affinity 
for  acid  coloring  matters  (eosin,  acid-fuchsin,  etc.),  hence  their 
name.  In  specimens  stained  with  eosin  or  eosin  and  methyl 
blue  they  are  very  brightly  colored  pink.  With  the  Ehrlich 
triacid  mixture  they  are  more  of  a  copper  or  burnt-sienna  color. 
Some  individual  granules  stain  much  darker  than  others  in  the 
same  cell,  and  may  be  of  a  different  nature. 

The  eosinophiles  are  the  most  actively  amosboid  of  all  the 
corpuscles,  and  it  may  be  for  this  reason  that  the  different  parts 
of  the  cell  seem  so  loosely  strung  together.  Or,  if  the  hy- 
pothesis of  Kanthack  and  Hardy,  recently  supported  by  Stokes, 
be  true  their  loose  arrangement  may  serve  to  make  them  easily 
detached  for  bactericidal  purposes  (see  above,  page  59) .  The 
granules  may  be  all  at  one  side  of  the  cell  and  the  nucleus  on 
the  other,  and  in  cover-glass  specimens  we  very  frequently  find 
actual  separation  of  the  two.  Whether  or  not  the  actual  sepa- 
ration is  brought  about  by  the  technique  of  spreading  the  blood 
is  unimportant,  as  we  find  such  broken  cells  much  more  often 
5 


66  CLINICAL   BLOOD    EXAMINATION. 

among  the  eosinophiles  than  among  any  other  variety— which 
argues  a  looser  structure. 

Sometimes  there  seem  to  be  two  or  more  distinct  and 
separate  nuclei  in  the  cell,  no  "  underground  connection"  being 
traceable.  The  granules  are  seldom  over  the  nucleus  as  we  see 
it  in  cover-glass  preparations,  but  cluster  round  it  loosely. 

The  cell  as  a  whole  is  usually  a  little  smaller  than  the  "  neu- 
trophile"  and  more  irregular  in  shape.  In  stained  specimens 
the  neutrophile  is  seldom  seen  with  a  pseudopod  extended, 
whereas  the  eosinophile  often  shows  it. 

The  staining  of  the  nucleus  is  more  even  as  well  as  paler 
than  that  of  the  neutrophile,  and  with  the  Ehrlich  stain  often 
has  a  robin' s-egg  tint.  To  sum  up: 

The  four  varieties  which  we  usually  find  among  leucocytes 
in  the  blood  are  these : 

1.  Small  lymphocytes,  or  "hyaline  cells." 

2.  Large  lymphocytes  and  transitional  forms. 

3.  Polymorphonuclear   neutrophiles,  or  fine  granular  oxy- 
philes. 

4.  Eosinophiles,  or  coarse  granular  oxyphiles. 

5.  A  fifth  variety  of  leucocyte — the  basophilic  "  mast  cell" — has  lately 
been  described  as  a  constituent  of  normal  blood,  though  in  very  small 
numbers.  In  leukaemia  it  is  very  common,  but  no  special  significance  is 
attached  to  it. 

With  Ehrlich's  stain  the  basophilic  granules  of  this  cell  are  not  seen  or 
appear  only  as  clear  white  spots.  Stained  with  the  following  solution 
they  are  easily  seen  : 

Dahlia  (saturated  alcoholic  solution  filtered) ,      .         .        .          50 
Glacial  acetic  acid,        .         .         ...        .        .         .     10-15 

Distilled  water,      .         .        ,         ....        .        v       .         100 

Covers  should  be  left  twenty-four  hours  in  this  mixture,  then  washed  and 
mounted  in  the  ordinary  way.  The  nucleus  is  usually  trilobed.  Though 
very  common  in  all  connective  tissue  as  well  as  in  the  wall  of  the  intestine 
and  the  serous  cavities,  these  cells  rarely  stray  into  the  circulating  blood. 

TEEMS. 

No  one  can  feel  more  unsatisfied  with  the  terminology  used 
in  this  book  than  the  writer.  It  rests  partly  on  a  theory  of  the 
origin  of  the  cells  ("lymphocytes"),  partly  on  the  properties  of 


FINER    STRUCTURE    OF   THE   BLOOD.  67 

the  nucleus  ("polymorphonuclear"),  and  partly  on  affinities  for 
aniline  dyes  ("  neutrophile" — "  eosinophile") . 

All  that  can  be  said  for  it  is  that  it  discards  certain  very 
misleading  names  like  "  splenocy  te"  (a  term  applied  by  some  to 
the  large  lymphocytes  according  to  the  now  exploded  theory 
that  they  come  from  the  spleen) ,  or  like  "  small  mononuclear" 
to  designate  cells  not  rarely  polynuclear. 

The  cumbrous  word  "  polymorphonuclear"  is  a  shade  better 
than  "polynuclear,"  and  that  is  all  to  be  said  in  its  favor. 

It  is  greatly  to  be  hoped  that  we  may  ere  long  have  a  new 
and  improved  terminology  by  some  competent  student.  The 
English  terms  above  referred  to  are  so  cumbrous  that  I  have  not 
as  yet  felt  compelled  by  their  slightly  greater  accuracy  to  adopt 
them  unconditionally,  but  they  certainly  show  a  tendency  in  the 
right  direction. 

For  some  unknown  reason  we  do  usually  find  the  leucocytes 
of  the  blood  only  in  these  four  forms  (the  frequent  presence  of 
transitional  stages  between  "small"  and  "large"  lymphocytes 
has  been  mentioned  as  an  exception).  There  are  far  too  few 
transitional  forms  between  the  four  varieties  to  be  seen  in  the 
circulating  blood  for  us  to  suppose  that  they  grow  from  one 
type  to  another  there.  It  may  be  that  they  all  have  a  common 
leucocyte  ancestor  and  are  "specialized"  in  various  extra- 
vascular  tissues  into  the  forms  which  we  meet  with  in  the 
blood.  There  seem  to  be  well-marked  sets  of  leucocyte  forms 
adapted  respectively  to  the  blood,  the  serous  spaces,  the  intes- 
tinal wall,  the  marrow,  the  connective  tissues,  and  the  adenoid 
tissues,  as  has  been  well  shown  by  recent  English  observations. 

NORMAL  PERCENTAGE  or  EACH  VARIETY. 

In  the  blood  of  healthy  adults  the  proportions  of  the  differ- 
ent varieties  above  described  are  the  following : 

,   ,    j  Small  lymphocytes, 20-30  per  cent. 

(  Large  "  4-8 

(6)  Polymorphonuclear  neutrophiles,         .         .  62-70        " 

(c)  Eosinophiles,         .......  £-4          " 

(d)  "Mast  cells,"         ......  tiri 

(a)  In  infancy  the  percentage  of  lymphocytes  is  much  larger 


68  CLINICAL   BLOOD    EXAMINATION. 

(forty  to  sixty  *  per  cent)  and  the  polymorphomiclear  neutro- 
philes  are  only  eighteen  or  forty  per  cent. 

In  a  variety  of  debilitated  conditions  not  usually  thought  of 
as  definite  diseases,  the  number  of  lymphocytes  is  comparatively 
large  and  that  of  the  polymorphonuclear  cells  small.  The 
general  vigor  and  health  of  the  individual  can  sometimes  be 
estimated  simply  from  the  leucocytes.  Persons  calling  them- 
selves well,  but  never  vigorous  or  active,  may  show  no  more 
than  fifty  per  cent  of  polymorphonuclear  cells,  the  lymphocytes 
running  up  to  forty  or  even  fifty  per  cent. 

Not  all  cases  of  debility  show  this  change,  and  we  are  not 
yet  in  a  position  to  say  under  just  what  conditions  it  occurs. 
It  certainly  is  not  peculiar  to  tuberculosis  as  Holmes  has  sup- 
posed. Presumably  the  conditions  are  such  as  decrease  the 
nutritive  value  of  the  plasma. 

(b)  Changes  in  the  percentage  of  neutrophiles  will  be  dis- 
cussed later. 

(c)  The  percentage  of  eosinophiles  often  changes  in  a  way  hard 
to  explain.     We  know  that  eosinophiles  are  present  in  large 
numbers  in  various  parts  of  the  body  outside  the  blood-vessels 
(bone  marrow,  gastro-intestinal  tract,  ccelomic  spaces,  thymus 
gland),  and  in  many  ways  they  seem  to  live  their  life  in  com- 
parative independence  of  the'  other  members  of  the  leucocyte 
group. 

In  the  free  interchange  of  fluid  and  cells  that  is  constantly 
going  on  between  blood-vessels  and  lymphatic  tissues  and 
spaces,  it  is  evident  that  a  part  of  the  life  history  of  the  leu- 
cocytes goes  on  outside  the  vessels,  and  there  is  reason  to  sup- 
pose that  it  is  chiefly  outside  the  vessels  that  cells  divide  and 
produce  others  like  themselves.  At  any  rate,  we  rarely  find 
evidence  of  mitosis  or  amitosis  in  the  circulating  leucocytes, 
while  in  the  lymph  glands  and  the  marrow,  and  elsewhere,  such 
dividing  forms  are  common. 

The  bone  marrow  seems  to  be  such  a  dividing-place  for 
eosinophiles.  They  are  always  numerous  there  and  mitoses  are 
often  seen  in  them.  Indeed  their  number  is  so  small  in  normal 
circulating  blood  that  they  might  almost  be  said  to  be  there 
"by  mistake,"  belonging  normally  elsewhere.  Whether  or  not 
this  has  any  connection  with  their  active  amoeboid  properties,  I 
do  not  know.  The  "  mast  cells"  are  even  more  "  an  accident"  in 


FINER   STRUCTURE   OF   THE   BLOOD.  69 

the  blood,  and  Ehrlich  denies  that  they  are  a  constituent  of 
normal  blood. 

The  increase  or  decrease  of  eosinophiles  in  the  circulating 
blood  does  not  follow  that  of  the  polymorphonuclear  neutro- 
philes,  in  fact  is  often  inversely  proportional  to  it,  and  the 
eosinophiles  are  often  markedly  increased  in  a  blood  otherwise 
normal,  for  reasons  wholly  unknown  to  us. 

An  increase  in  the  lymphocytes  or  neutrophiles  does  not 
occur  without  other  blood  changes,  and  points,  not  to  disease 
of  one  place  or  function,  but  to  general  conditions  like  inflam- 
mation or  malnutrition.  The  diagnostic  indications  of  an  in- 
crease of  the  eosinophiles  are  more  specific  (vide  infra,  articles 
"Trichinosis,"  "Asthma,"  "Dermatitis  Herpetif ormis, "  etc.). 

I  have  spoken  of  the  eosinophiles  and  "  mast  cells"  as  com- 
parative strangers,  though  not  intruders  in  the  circulating  bood. 
They  are  thus  intermediate  between  the  regular  inhabitants 
(lymphocytes  and  neutrophiles)  and  the  variety  next  to  be  men- 
tioned, which  are  real  intruders — i.e.,  never  found  in  normal 
blood.  These  are  the 

MYELOCYTES  (EHRLICH). 

The  normal l  abiding-place  of  these  cells  appears  to  be  the 
bone  marrow,  hence  their  name  of  myelocytes  or  marrow  cells. 
They  are  perhaps  the  most  numerous  leucocytes  to  be  found  in 
the  marrow,  although  lymphocytes  and  polymorphonuclear  cells 
are  also  to  be  found  there,  and  eosinophiles  and  basophiles  are 
numerous. 

I  describe  them  here  because  they  are  peculiar  to  no  one  dis- 
ease and  are  occasional  visitors  of  the  blood  in  various  diseased 
conditions  and  in  conditions  on  the  borderland  between  the 
pathological  and  the  physiological  (starvation — various  intoxi- 
cations) . 

The  myelocyte   (see  Plate  L),  like  the  polymorphonuclear 

'Frankel  (15th  Congresse  fur  innere  Med.,  1897)  has  reported  the  find- 
ing of  myelocytes  in  the  swollen  lymph  glands  of  a  case  of  scarlet  fever. 
In  leukaemia  they  are  found  in  the  metastases  and  infiltrations  in  various 
organs  as  well  as  in  the  blood.  Otherwise  they  are  confined  to  the  marrow 
so  far  as  I  know,  except  that  very  small  numbers  may  enter  the  blood  in 
conditions  involving  leucocytosis  or  grave  anaemia. 


70  CLINICAL  BLOOD   EXAMINATION. 

neutrophile,  is  recognizable  only  by  Ehrlich's  staining  methods. 
With  Ehrlich's  triple  stain  it  appears  as  a  spherical  cell  nearly 
filled  by  a  large,  pale-stained  nucleus  immersed  in  neutrophilic 
granules.  One  sees  at  once  how  little  it  differs  from  the  large 
lymphocytes  (simply  in  having  granules)  and  from  the  poly- 
morphonuclear  neutrophile  (only  in  the  shape  of  its  nucleus). 
Were  it  present  in  normal  blood  we  should  undoubtedly  con- 
sider it  an  intermediate  stage  between  the  large  lymphocyte  and 
the  polymorphonuclear  neutrophile.  I  see  no  sufficient  reason 
for  thinking  otherwise  merely  because  it  does  not  appear  in 
normal  blood.  The  leucocytes  are  so  cosmopolitan  in  their 
habits  that  we  can  hardly  call  them  blood  cells  at  all.  It  is 
better  to  think  of  "blood  leucocytes,"  "gland  leucocytes,"  and 
"marrow  leucocytes"  (perhaps  "skin  and  mucous  membrane 
leucocytes"  too,  see  page  117)  and  to  consider  that  "  missing 
links"  among  blood  leucocytes  are  to  be  looked  for  among 
those  that  live  and  grow  up  elsewhere.  Perhaps  the  condi- 
tions in  the  marrow  (rest,  nutrition?)  are  such  as  bring  out 
sides  of  the  leucocyte  nature  suppressed  in  the  blood.  Staining 
with  eosin  and  methylene  blue  shows  that  myelocytes  also  con- 
tain fine  basophilic  (blue)  granules.  The  suggestion  of  their 
transitional  nature  is  thereby  increased,  since  they  have  baso- 
phile  granules  in  common  with  the  lymphocytes,  and  neutrophile 
granules  in  common  with  the  polymorphonuclear  cells.  I  am 
indebted  to  Dr.  H.  F.  Hewes  for  calling  my  attention  to  this 
point.  With  Ehrlich's  stain  the  granules  of  the  myelocyte  are 
precisely  those  of  the  polymorphonuclear  leucocyte  and  need  no 
second  description  (see  Plate  I.).  The  nucleus,  by  which  alone 
we  distinguish  the  myelocyte,  shows  none  of  the  twists  and 
turns  characteristic  of  the  polymorphonuclear  neutrophile,  but 
is  usually  spherical  or  egg-shaped,  and  is  in  close  contact  with 
the  cell  wall  for  a  comparatively  large  portion  of  its  extent — 
i.e.,  if  egg-shaped  it  is  placed  eccentrically. 

Not  infrequently  the  nucleus  shows  signs  of  old  age 
(vacuoles)  or  of  mitosis,  for  not  infrequently  we  find  two  nuclei 
at  the  poles  of  the  cell.  It  is  then  to  be  distinguished  from  the 
polymorphonuclear  neutrophile  by  the  fact  of  its  having  the 
nuclei  in  close  contact  with  the  surface  of  the  whole  cell  for  a 
comparatively  large  portion  of  their  extent,  while  in  the  poly- 
morphonuclear leucocyte  the  nucleus  abruptly  leaves  the  sur- 


FINER   STRUCTURE   OF   THE   BLOOD.  71 

faces  again  if  it  chances  to  approach  it.  The  dividing  myelo- 
cyte is  also  to  be  distinguished  from  the  polymorphonuclear 
neutrophile  by  the  even  staining  of  the  nucleus  in  the  former. 

Size  of  Myelocytes. 

Almost  every  account  of  the  myelocyte  which  has  come  to 
my  notice  speaks  of  it  as  a  very  large  cell,  the  largest  variety  of 
leucocyte  ever  seen  in  the  blood. 

This  is  true  of  many  of  them ;  diameters  of  18-21  P.  are  not 
uncommon,  but  we  also  find  them  of  every  other  size  down  to 
10-11  fj.  diameter,  that  is,  down  to  the  size  of  a  lymphocyte. 
This  is  true  both  of  the  myelocytes  in  the  circulating  (leukgemic) 
blood  and  of  those  in  the  marrow.  No  distinction  from  other 
varieties  of  leucocyte  can  be  based  on  size  alone,  unless  we  say 
their  average  size  is  greater  than  the  average  size  of  the  leu- 
cocyte. Perhaps  the  following  table  may  be  of  interest: 

Average  diameter  of  100  myelocytes  =  15.75  n. 

"  "         "  100  poly  morphonuclearneutroph  lies  =  13.50  p. 

«  "         "   100 "large"  lymphocytes  =  13  u. 

a  "         "   100  eosinophiles  =  12  ju. 

tt  *'••'*  100  "small"  lymphocytes  =  10  ft. 

tt  u         u   100  red  corpuscles  (normal)  =7.5  ;w. 

EOSINOPHILIC  MYELOCYTES. 

Under  the  same  conditions  where  we  expect  to  find  the  or- 
dinary (neutrophilic)  myelocyte,  we  often  find  a  small  number 
of  cells  identical  with  them  in  all  respects,  except  in  possessing, 
eosinophilic  in  place  of  neutrophilic  granules.  Such  cells  are 
found  in  abundance  in  the  marrow,  and  this  fact  together  with 
the  resemblance  to  the  ordinary  myelocyte  both  in  morphology 
and  in  the  conditions  of  their  occurrence,  seems  to  me  to  justify 
the  term  eosinophilic  myelocyte. 

COBNIL'S  "MARK  CELLS." 

By  most  observers  these  are  supposed  to  be  the  same  as 
Ehrlich's  "mark  cells"  or  myelocytes.  Cornil  worked  before 
the  days  of  Ehrlich's  staining  methods  and  therefore  before  the 
presence  of  neutrophilic  granules  could  be  used  to  distinguish  a 


72  CLINICAL   BLOOD   EXAMINATION. 

myelocyte  from  a  large  lymphocyte.  Corral's  description  of 
them  would  answer  for  either.  Schreiber  considers  Cornil  to 
Lave  discovered  a  different  variety  of  non-granular  cell,  but  the 
description  of  it  given  by  Schreiber  seems  to  me  to  leave  it  in- 
distinguishable from  a  large  lymphocyte. 

Mononuclear  Neutrophiles. — Capps1  observed  in  general  paralysis  of 
the  insane  a  variety  of  leucocyte  possessing  a  deep-staining  centrally 
placed  nucleus  like  that  of  a  lymphocyte,  but  containing  also  neutrophilic 
granules.  He  considers  it  either  a  variation  from  the  ordinary  type  of 
marrow-bred  cell  visiting  the  blood  temporarily,  or  more  likely  an  ordi- 
nary lymphocyte  in  which  the  granules  have  developed  before  the  nucleus 
has  become  polymorphous.  Thayer  has  observed  similar  cells,  but  has 
given  no  explanation  of  them.  Klein2  mentions  them  under  the  name 
above  given  and  figures  them  in  his  plates,  but  does  not  comment  on  them. 
I  am  inclined  to  think  them  ordinary  myelocytes. 

So  far  I  have  described  the  type  cell  of  each  variety.  As  we 
should  expect,  atypical  forms  are  numerous.  Some  of  the  com- 
moner ones  are  as  follows : 

1.  Small  lymphocytes  whose  nucleus  is  pale  blue  instead  of 
dark  blue. 

2.  Large  lymphocytes,  whose  protoplasm  has  evidently  for- 
saken them  (degeneration  forms,  often  more  or  less  deformed  or 
tattered) . 

3.  Cells  on  the  borderland  between  the  "marrow  cell"  and  the 
"  poly morphonuclear  leucocyte, "  the  nucleus  having  some  of  the 
characters  of  each  variety. 

4.  Cells  tiie  nature  of  whose  granules  we  cannot  settle  (eosi- 
nophilic  or  neutrophilic). 

Other  rare  varieties  will  be  mentioned  under  leukaemia. 

1  American  Journal  of  Medical  Sciences,  June,  1896. 

2  Volkmanu's  Sammlung  klin.  Vortrage,  December,  1893. 


PART  III. 

GENERAL  PATHOLOGY  OF  THE  BLOOD. 


CHAPTER  VI. 

UNEQUAL     DISTRIBUTION    OF     BLOOD— PLETHORA— DILUTION 
AND  CONCENTRATION  OF  THE   BLOOD. 

I.    Unequal  Distribution. 

How  far  is  the  single  drop  used  for  blood  examination  typi- 
cal of  the  whole? 

It  has  been  experimentally  proved  that  specimens  of  the 
blood  of  the  smaller  venous  and  arterial  twigs  do  not  differ 
from  each  other  materially  in  corpuscular  richness.  Capillary 
blood  is  slightly  richer  in  corpuscles  than  that  either  of  veins 
or  of  arteries.  But  as  capillary  blood  is  everywhere  of  the 
same  corpuscular  richness,  we  may  consider  one  capillary  net- 
work or  set  of  venules  as  typical  as  another,  provided  our  tech- 
nique is  good,  that  is,  provided  lymph  is  not  squeezed  into  the 
drop  by  strong  pressure.  It  is  indifferent,  therefore,  so  far  as 
accuracy  is  concerned,  whether  the  drop  of  blood  be  obtained 
from  one  or  another  part  of  the  body.  All  standard  estimates 
of  the  number  of  corpuscles  per  cubic  millimetre  of  normal 
blood  refer  to  capillary  blood. 

2.    Apparent  Polycyihcemia. 

So  far  we  are  speaking  of  normal  conditions.  It  is  a  famil- 
iar fact,  however,  that  the  vessels  of  a  given  part  of  the  body 
can  be  overcrowded  with  blood,  e.g.,  by  the  use  of  an  Esmarch 
bandage.  A  drop  taken  from  such  a  part  would  certainly  not 
be  typical.  Now  as  the  same  effect  can  be  produced  by  a 
variety  of  diseases,  under  these  conditions  we  must  modify 
considerably  any  inferences  made  from  examination  of  a  single 
drop. 


74  CLINICAL   BLOOD   EXAMINATION. 

Such  conditions,  entailing  a  false  polycythaemia  or  apparent 
increase  in  the  number  of  corpuscles  are : 

I.  Any  disease  involving  either  (a)  general  cyanosis  or  (6) 
cyanosis  of  the  part  from  which  the  drop  of  blood  is  drawn. 

(a)  General  cyanosis  results  either  from  cardiac  insufficiency 
(valvular  or  parietal  disease  of  the  heart  itself,  blocking  of  the 
lung  circulation  by  emphysema  or  thrombosis),  from  insufficient 
aeration  of  the  blood  (pneumonia,  congenital  malformation  of 
the  heart),  interference  with  the  heart's  action  by  pressure  of 
tumors,  effusions  (pericardial,  pleural,  peritoneal),  or  enlarged 
organs  (liver,  spleen),  or  from  vasomotor  disturbances.     It  is 
evident  that  some  of  these  conditions  (e.g.,  congenital  heart 
disease)  may  not  involve  any  peripheral  stasis  at  all,  and  in  the 
absence  of  this  it  is  not  easy  to  account  for  the  increased  number 
of  corpuscles  in  the  drop.     Some  observers  have  supposed  that 
there  is  a  real  overproduction  of  blood  cells  under  these  condi- 
tions ;  others  suppose  that  the  life  of  the  individual  corpuscle 
being  lengthened,  reproduction  of  cells  at  the  normal  rate  soon 
leads  to  the  "glut."     There  seems  to  be  no  reason  to  suppose 
that  there  is  in  these  cases  any  unequal  distribution  of  cells  in 
favor  of  the  peripherj^,  such  as  is  obviously  the  condition  in 
ordinary  cyanosis  with  stasis.     Whatever  the  explanation  may 
be,  there  is  no  doubt  of  the  fact  that  general  cyanosis  from  any 
cause  whatever  produces  an  increase  of  cells  in  a  drop  such  as 
we  usually  examine. 

The  cases  of  cyanosis  which  I  have  classed  under  "  vaso- 
motor" (for  want  of  a  better  explanation),  cases  in  which,  in  the 
absence  of  disease  in  any  organ,  the  skin  and  mucous  mem- 
branes are  persistently  and  markedly  bluish,  are  not  very 
uncommon.  I  have  seen  three  such,  all  in  stout,  elderly 
women.  In  one  the  cells  in  a  drop  of  blood  from  the  ear, 
finger,  or  toe  were  more  than  double  the  normal  number  (see 
below,  page  81). 

(b)  Local  Cyanosis. — The  pressure  of  a  tumor,  or  any  other 
hindrance  to  the  circulation  of  any  part,  may  give  a  similar  in- 
crease in  the  number  of  corpuscles  in  a  measured  amount  of 
blood  from  that  part.     Here  again  vasomotor  conditions  may 
cause  cyanosis  and  apparent  polycythsemia. 

In  markedly  cyanotic  patients  the  count  of  red  cells  is  notably 
above  normal,  we  should  naturally  guess  the  reason,  and  make 


GENERAL  PATHOLOGY  OF  THE  BLOOD.          75 

allowances.  Error  is  more  likely  to  arise  where  we  have  cyanosis 
in  a  person  whose  blood  is  poor  in  red  corpuscles.  The  combi- 
nation of  these  two  factors  may  give  us  a  normal  blood  count  and 
lead  us  to  overlook  the  anaemia.  Thus  a  person  might  have 
really  a  severe  anaemia  and  yet  the  count  of  red  cells  be  actually 
above  the  normal.'  This  element  of  stasis  should  never  be  lost 
sight  of.  Many  high  counts  reported  in  pneumonia  or  hysteria 
are  to  be  explained  by  abnormalities  not  of  production  or  destruc- 
tion but  of  distribution  of  the  blood  cells. 

II.  Certain  patients,  whoso  circulations  are  feeble  without 
being  feeble  enough  to  produce  actual  cyanosis,  first  give  us- 
evidence  of  the  fact  by  an  increase  in  the  count  of  blood  corpus- 
cles in  a  given  amount  of  peripheral  blood.  Following  up  the 
hint  thus  given,  one  may  sometimes  be  brought  to  note  and  in- 
vestigate an  element  in  the  case  which  might  otherwise  have- 
been  lost  sight  of. 

"With  these  exceptions  the  drop  of  blood  taken  at  the  periph- 
ery is  typical.  We  have  next  to  consider  some  general  condi- 
tions under  which  a  person's  whole  blood  may  be  inferred  to  be 
abnormal  from  the  findings  in  a  drop  taken  from  the  periphery. 
Consideration  of  special  diseases  will  follow  later. 

FULL-BLOODEDNESS  (PLETHORA)  AND  ITS  OPPOSITE. 

There  is  no  direct  evidence  for  the  existence  of  any  long- 
standing over-filling  or  under-filling  of  the  blood-vessels ;  there 
is  a  good  deal  of  experimental  evidence  to  show  that  if  by  arti- 
ficial means  we  succeed  in  forcing  into  the  vessels  an  abnormal 
amount  of  fluid  (transfusion  of  blood  or  normal  salt  solution — 
large  draughts  of  water),  it  does  not  stay  there  many  hours,  but 
comes  out  by  the  kidneys. 

The  red-faced  persons  popularly  known  as  "full-blooded" 
show  no  abnormalities  in  their  blood  discoverable  by  any  means 
of  investigation  known  to  us.  The  condition  is  probably  de- 
pendent on  the  presence  of  a  rich  capillary  network  near  the 
surface  of  the  skin,  or  a  dilatation  of  individual  venules  and 
arterioles  at  the  periphery.  Such  a  person  may  be  markedly 
anaemic  without  any  considerable  changes  in  the  color  of  the 
face.  The  fact  that  people  of  such  complexion  often  end  their 
lives  with  a  ruptured  cerebral  artery  is  due  presumably  to  the- 


76  CLINICAL   BLOOD   EXAMINATION. 

circumstance  that  "  high  living"  produces  in  the  same  individual 
dilated  peripheral  capillaries  and  weakened  arterial  walls. 

Temporary  increase  or  diminution  in  the  amount  of  fluid  with- 
in the  vessels  can  be  brought  about  not  only  by  a  change  in  the 
mechanical  conditions  of  pressure  and  osmosis,  but  by  any  influ- 
ence affecting  the  tone  of  the  peripheral  vessels.  We  have  then: 

(a)  Temporary  serous  plethora  or  dilution  of  the  blood  from 
transfusion  of  fluid  in  large  amounts  or  its  ingestion  by  mouth 
or  rectum. 

(b)  From  decreased  blood  pressure,  as  in  acute  failures  of 
compensation  in  cardiac  disease. 

(c)  From  vasomotor  dilatation. 

As  an  example  of  this  last  Grawitz  reduced  the  specific  grav- 
ity of  the  blood  from  1041  to  1038.7  within  eight  minutes  by 
the  inhalation  of  nitrite  of  amyl.  This  decrease  of  specific  grav- 
ity can  only  mean  an  increased  amount  of  watery  constituents  in 
the  blood,  as  there  was  no  evidence  of  any  destruction  of  the 
heavier  elements  of  the  blood,  and  only  water  (and  chlorides) 
pass  through  the  vessel  walls  easily.  In  the  above  case  the 
specific  gravity  was  again  at  1041  within  a  few  minutes. 

(d)  In  cases  of  severe  anaemia  which  recover,  the  blood  regen- 
eration may  attain  such  vigor  that  the  number  of  red  cells  shoots 
up  above  normal,  even  as  high  as  7,700,000.     This  is  temporary 
cellular  plethora  or  polycythsemia. 

(e)  The  same  condition  can  be  temporarily   produced  by 
transfusion  of  actual  blood  from  one  individual  to  another.     It 
lasts  but  a  few  days  as  a  rule. 

The  polycythsemia  of  the  new-born  will  be  discussed  later. 

Concentration  of  the  Blood. 

It  is  obvious  that  influences  opposite  to  those  producing 
temporary  full-bloodedness  will  produce  temporary  lack  of  fluid 
within  the  vessels.  So  acute  diarrhoea,  purgation,  deprivation 
of  liquids  (as  in  starvation),  rapidly  accumulated  serous  effu- 
sions, profuse  vomiting  or  sweating  (by  skin  and  lungs)  produce 
a  temporary  concentration  of  the  blood  by  draining  out  its  diffus- 
ible elements  (water  chiefly) .  All  these  influences  are  transitory. 
More  permanent  drains  on  the  system,  like  chronic  diarrhoea, 
diabetes  insipidus  or  nielli tus,  or  long-standing  suppurations, 
show  no  evidence  of  lessening  the  volume  of  blood  in  the  vessels. 


GENERAL  PATHOLOGY  OF  THE  BLOOD.          77 

They  drain  albumin  out  of  the  serum  and  corpuscles  and  so 
decrease  the  weight  of  the  blood  (see  below,  page  85) ,  but  the 
blood  volume  is  not  changed.  Indeed,  any  influence  has  to  work 
very  quickly  in  order  to  concentrate  the  blood,  for  in  an  aston- 
ishingly short  time  the  other  tissues  repay  the  vessels  their  loss 
of  fluid  and  the  normal  blood  volume  is  restored. 

The  same  temporary  effects  can  be  produced  by  influences  con- 
stricting the  vessels  (cold,  pain,  suprarenal  extract) ,  and  a  concen- 
tration of  the  blood  results  which  lasts  a  few  minutes  or  hours.1 

In  all  these  interchanges  of  contents  between  the  blood- 
vessels and  the  other  tissues  it  is,  as  above  said,  the  watery  ele- 
ments chiefly  that  change.  The  red  cells  are  not  affected  by  the 
give-and-take  of  the  vessels  and  tissues,  and  although  cold  pro- 
duces in  the  peripheral  circulation  an  increase  in  the  number  of 
white  cells  greater  than  can  be  accounted  for  by  simple  Concen- 
tration, the  weight  of  evidence  seems  to  be  against  any  new  pro- 
duction of  cells  and  in  favor  of  a  change  only  in  distribution, 
the  white  cells  accumulating  at  the  periphery. 

Now  as  the  number  of  cells  is  not  affected  by  these  tempo- 
rary variations  in  the  volume  of  liquid  within  the  vessels,  it  fol- 
lows that  the  number  to  be  counted  in  a  cubic  millimetre,  though 
typical  of  the  whole  blood  at  that  time,  is  not  to  be  reckoned  from 
in  the  ordinary  way.  For  example,  after  a  severe  diarrhoea  or  in 
phthisis  after  a  night-sweat  the  blood  may  be  temporarily  so 
concentrated  that  we  find  6,000,000  or  more  red  corpuscles  per 
cubic  millimetre.  Under  normal  conditions  of  the  blood  mass 
we  should  infer  from  such  a  count  that  the  body  contained  one- 
sixth  more  red  corpuscles  than  usual.  Here  obviously  it  only 
means  (if  anaemia  is  absent)  that  the  blood  mass  is  reduced  by 
one-sixth  by  concentration.  It  is  only  in  such  sudden  reduc- 
tions of  blood  volume  that  we  can  measure  the  amount  lost  by 

1  Oliver  has  shown  recently  (Lancet,  June  27th,  1896)  that  any  influence 
causing  rise  of  blood  pressure  will  slightly  concentrate  the  blood.  Thus 
raising  the  arm  over  the  head  and  holding  it  there  by  muscular  effort 
slightly  concentrates  the  blood  in  that  arm.  Electrical  stimulation  or 
massage  of  the  arm  has  the  same  effect.  Lowering  blood  pressure,  as 
when  the  arm  is  supported  passively  over  the  head,  dilutes  the  blood.  This 
confirms  the  results  of  Mitchell  (Med.  News,  May,  1893)  and  of  Cheron 
(Comptes  Rend,  de  1'Acad.  d.  Sciences,  1896,  No.  vi.).  Oliver  uses  a 
new  method  for  estimating  the  number  of  red  cells,  the  accuracy  of  which 
has  not  yet  been  tested  by  others  (see  above,  page  27) . 


78  CLINICAL   BLOOD    EXAMINATION. 

this  method.  Long-standing  causes  of  drain  on  the  plasma 
might  at  any  time  act  as  destroyers  of  red  corpuscles  as  well, 
through  the  changes  in  the  nutritive  fluids  in  which  they  live. 

Further,  it  is  only  where  we  know  the  number  of  corpuscles 
just  before  the  sudden  drain  on  the  plasma  comes,  that  we  can 
measure  the  amount  of  plasma  lost  by  the  amount  of  apparent 
increase  in  the  red  cells.  Stasis  and  any  other  cause  that  heaps 
up  corpuscles  at  the  periphery  must  also  be  excluded  before  we 
can  judge  of  the  loss  of  plasma  in  this  way. 

The  conditions  of  an  abnormal  concentration  of  the  blood  are 
those  already  alluded  to  as  temporarily  sucking  away  its  watery 
constituents,  namely: 

(a)  Watery  diarrhoea,  especially  in  cholera  and  other  acute 
diseases  accompanied  by  diarrhoea ; 

(6)  Large  and  rapidly  accumulating  serous  effusions  (slow 
accumulations  would  give  time  for  the  blood  to  take  up  water 
from  the  tissues  and  make  up  for  its  loss) ; 

(c)  Profuse  sweats; 

(d)  Persistent  vomiting  or  starvation  of  liquids ; 

(e)  Increased  blood  pressure  (exercise,  massage,  electricity). 
Blood  already  lacking  in  red  cells,  if  suddenly  concentrated 

by  such  a  loss  of  fluid,  might  deceive  us  into  supposing  it 
normal,  because  the  number  of  cells  in  a  cubic  millimetre  might 
be  normal.  In  the  presence,  therefore,  of  any  such  reason  for 
concentration  of  the  blood,  we,  should  always  modify  our  ordi- 
nary methods  of  inference  from  the  Hood  count.  For  example, 
v.  Limbeck  records  a  case  of  hepatic  cirrhosis  with  ascites, 
where  before  tapping  the  ascites  the  count  of  red  cells  was 
3,280,000  per  cubic  millimetre.  Within  twenty-four  hours  after 
tapping  there  were  5,160,000  cells  per  cubic  millimetre,  the 
reaccumulation  of  the  ascitic  fluid  going  on  so  fast  that  the 
blood  was  unable  to  adjust  itself  and  became  overconcentrated. 
A  careless  observation  might  have  inferred  a  great  gain  in  the 
corpuscular  richness  of  the  whole  blood,  when  in  fact  not  a  cor- 
puscle has  been  gained  and  those  present  have  probably  grown 
poorer  in  albumin. 

Dilution  of  the  Blood. 

Causes  of  temporary  dilution  of  the  blood  are  less  common 
than  those  of  temporary  concentration. 


GENERAL  PATHOLOGY  OF  THE  BLOOD. 


79 


Immediately  after  the  inhalation  of  nitrite  of  amyl  or  the  in- 
gestion  of  a  large  amount  of  fluid  by  mouth  or  rectum,  the  blood 
would  be  diluted  so  that  a  blood  count  would  show  a  diminu- 
tion in  the  number  of  cells  per  cubic  millimetre,  which  yet 
would  be  due  to  no  changes  in  the  number  of  red  cells  in  the 
body,  and  might  be  wrongly  taken  for  an  anaemia.  The  dilu- 
tion in  cases  of  heart  disease  will  be  discussed  later  (see  p.  296). 
Any  condition  involving  loivered  blood  pressure  has  the  effect  of 
diluting  the  blood  by  allowing  the  entrance  of  perivascular 
lymph. 

Summing  up  the  discussion  so  far :  There  is  no  evidence  for 
a  chronic  plethora  nor  for  a  chronic  diminution  in  the  volume  of 
the  blood.  Where  such  takes  place  temporarily,  it  is  by  the  ad- 
dition or  subtraction  of  water  and  salts  only,  and  not  of  the  cor- 
puscles or  organic  materials,  so  that  we  must  guard  against  false 
inferences  from  the  resulting  apparent  increase  or  decrease  of 
corpuscles  per  cubic  millimetre. 

But  although  there  is  no  positive  evidence  of  a  true  increase 
in  the  whole  amount  of  blood  in  the  vessels  (except  temporarily) , 
there  are  some  conditions  which  lead  to  an  increased  richness  of 
the  peripheral  blood  in  red  corpuscles  even  after  excluding  the 
influence  of  stasis  or  loss  of  fluid.  Such  a  condition  of  what 
appears  to  be  true  polycythaemia  is  found: 

1.  In  persons  living  at  high  altitudes; 

2.  In  persons  suffering  from  phosphorus  or  CO  poisoning. 

1.    The  Slood  in  High  Altitudes. 

The  polycythsemia  of  those  living  at  high  altitudes  increases 
the  higher  one  goes.  Koppe  '  gives  the  following  tables : 


Place. 

Height  above 
sea  level. 

Red  cells. 

Author. 

Christiania. 

o 

4  974  000 

Laache. 

Gottingen  

148  metres 

5,225  000 

Schafer. 

Tubingen  .... 

314       " 

5,322  000 

Reinert. 

Zurich  

414       " 

5,  752,  000 

Stierlin. 

Auerbach 

425       " 

5  748  000 

Koppe 

Reiboldsgriin  . 

700       " 

5  900  000 

Arosa  

1  800       " 

7  000  000 

Eerier. 

The  Cordilleras  

4  392       " 

8  000  000 

Viault 

1  Munch,  raed.  Woch.,  1890,  No.  41. 


80  CLINICAL   BLOOD   EXAMINATION. 

This  extraordinary  change  takes  place  within  two  weeks  of 
the  time  of  taking  up  residence  in  a  high  place,  and  independent 
of  any  change  in  diet  or  manner  of  living.  The  sick  and  the 
well  are  equally  affected  and  animals  show  similar  changes. 
The  haemoglobin  is  also  considerably  increased,  although  it  lags 
somewhat  behind  the  corpuscles. 

Koppe  states  that  the  individual  corpuscles  under  these  con- 
ditions are  so  much  smaller  that  their  volume  in  a  given 
amount  of  blood  (as  determined  by  the  hsematocrit)  is  not  in- 
creased at  all. 

On  returning  to  low  land,  the  blood  returns  within  a  short 
time  to  its  normal  condition. 

Many  explanations  have  been  offered  for  this  interesting 
phenomenon.  If  it  were  a  true  new  production  of  corpuscles  we 
should  expect  some  signs  of  blood  destruction  (icterus,  hsemo- 
globinuria)  on  returning  to  the  sea  level.  But  there  are  no  such 
signs.  On  the  other  hand,  if  the  polycythaemia  were  a  simple 
result  of  concentration  due  to  the  dryness  of  the  high  air,  one 
would  expect  that  the  blood  would  quickly  adapt  itself,  as  in 
other  (temporary)  concentrations,  by  taking  up  water  from  the 
tissues.  But  in  fact  it  does  not  do  so.  The  cause  of  the  in- 
crease is  still  a  mystery. 

2.  PhospJiorus  and   CO  Poisoning. 

The  polycythsemia  of  acute  phosphorus  poisoning  may 
reach  as  high  as  8,650,000.  This  may  be  partly  explained  by 
concentration  due  to  the  occurrence  of  vomiting,  but  in  some 
cases  the  increase  seems  out  of  proportion  to  the  amount  of 
vomiting. 

With  illuminating-gas  poisoning  there  is  usually  no  vomiting 
to  speak  of,  and  the  cause  of  the  marked  increase  in  the  red 
cells  is  unknown.  Von  Limbeck  in  two  cases  of  CO  poisoning 
showed  respectively  6,630,000  and  5,700,000  red  cells.  Miinzer 
and  Palma1  record  5,700,000.  The  white  cells  are  also  in- 
creased (see  page  330). 

Possibility  of  a  True  Plethora. 

Although  there  is  no  direct  evidence  that  the  whole  blood 
mass  in  its  relation  to  the  weight  of  the  body  ever  varies  more 
'Zeit.  f.  Heilk.,  vol.  15,  p.  1. 


GENERAL  PATHOLOGY  OF  THE  BLOOD.          81 

than  temporarily  from  the  traditional  1  to  13,  one  cannot  help 
getting  the  impression  in  some  cases  that  the  blood  mass  is 
increased  or  diminished,  though  we  cannot  prove  it.  Thus  in 
certain  cases  of  phthisis  in  which  in  spite  of  all  the  signs  and 
symptoms  of  anaemia  the  blood  count  is  normal,  and  simple  con- 
centration of  a  really  anaemic  blood  seems  to  be  excluded  by 
the  absence  of  a  cause  for  such  concentration,  we  cannot  help 
thinking  that  the  whole  amount  of  blood  is  too  small.  Again, 
it  is  possible  that  in  individuals  who  eat  and  drink  much  and 
exercise  little  the  blood-vessels  may  gradually  accommodate 
themselves  so  as  to  hold  a  large  bulk  of  liquid,  and  thus  a  true 
plethora  or  "  full-blooded"  condition  might  be  brought  about. 
Experiments  show,  however,  that  fat,  "sedentary"  animals 
(pigs)  have  less  blood  in  proportion  to  their  weight  than  lean, 
active  animals  (horses,  dogs).  Pigs'  blood  is  only  one  twenty- 
second  of  their  total  weight,  while  horses'  is  one-tenth. 

I  have  repeatedly  examined  the  blood  in  two  patients  with 
chronic  cyanosis  without  known  cause  and  found  from  8,000,000 
to  9,000,000  corpuscles  in  each  case.  One  of  these  patients 
died  of  cerebral  hemorrhage,  and  the  autopsy  revealed  no  lesions 
whatever  except  a  stuffing  of  all  the  internal  organs  with  blood 
and  the  results  of  chronic  passive  congestion  everywhere.  This 
certainly  seems  like  a  true  plethora. 

Young,  fast-growing  animals  have  relatively  more  blood  than 
adults,  and  males  more  than  females.  Our  impression  that  old 
people  are  more  or  less  "  dried  up"  gets  some  support  from  the 
analogy  of  these  animal  experiments. 

Until  some  method  is  devised  for  estimating  the  total  amount 
of  blood  during  life,  we  shall  never  be  sure  upon  this  point. 
6 


CHAPTEK  VII. 


ANJEMIA  AND  HYDR^EMIA. 

1.  ANEMIA. 

IN  the  absence  of  any  proof  that  the  total  volume  of  blood 
can  be  more  than  temporality  diminished,  our  definition  of 
anaemia  must  be  this:  A  deficiency  in  corpuscle  substance)  i.e., 
a  deficiency  in  red  corpuscles,  in  haemoglobin,  or  in  both. l 

It  is  important  to  bear  in  mind  that  the  color  of  the  skin  is 
not  a  safe  guide  in  judging  whether  a  person  is  anaemic.  Thus 
out  of  100  cases  shown  to  be  anaemic  by  actual  blood  examina- 
tion, Townsend8  found  a  good  color  in  the  cheeks  of  4  and  a 
fair  color  in  7  others.  Eighty-nine  were  pale.  The  color  of 
the  lips  is  but  little  better  as  a  guide,  as  the  following  table 
from  Townsend' s  article  shows : 

Table  of  Color  in  One  Hundred  Cases  of  Ancemia. 


Pale. 

Fair. 

Good. 

Nails  

95 

5 

0 

Cheeks  

89 

7 

4 

Tongue  

84 

15 

1.2 

Lips  

76 

21 

2.4 

Conjunctivas                  

64 

25.5 

10.5 

My  own  impression  would  be  that  the  lips  and  conjunctivae 
were  better  guides  than  they  are  shown  to  be  in  this  table. 

In  examining  the  color  of  the  nails,  the  fingers  should  be 
flexed,  as  full  extension  may  partly  cut  off  the  circulation  under 
the  nails. 

1  This  is  a  clinical  definition  and  makes  no  attempt  to  go  to  the  root  of 
the  matter.     I  have  little  doubt  that  chemical  or  other  changes  in  the 
serum  are  the  cause  of  the  corpuscular  changes,  which  only  mirror  the 
deeper  disease.     But  these  chemical  changes  are  as  yet  so  little  understood 
that  we  have  to  judge  of  their  presence  chiefly  by  their  effect  on  the  cor- 
puscles. 

2  Townsend  :  Boston  Medical  and  Surgical  Journal,  May  28th,  1896. 


ANAEMIA  AND    HYDR^MIA.  83 

A.  K.  Stone  l  and  his  assistants  estimated  the  haemoglobin 
of  189  female  patients  who  looked  anaemic,  and  found  over  75 
per  cent  of  haemoglobin  in  89,  or  nearly  one-half  of  them.  For 
a  woman  a  haemoglobin  percentage  of  75  per  cent  or  more 
means  practically  normal  blood.8 

The  most  striking  example  of  the  fallacy  of  judging  of 
anaemia  by  the  color  of  the  skin  and  mucous  membranes  is  in 
the  so-called  "  tropical  ancemia"  Practically  all  persons  belong- 
ing to  white  races  who  take  up  their  residence  in  the  tropics 
acquire  after  a  time  an  extreme  pallor  of  the  skin  and  mucous 
membranes,  and  this  appearance  has  usually  received  the  title  of 
"tropical  anaemia."  It  turns  out,  however,  from  the  careful 
studies  of  several  different  investigators,  that  the  blood  of  such 
persons  shows  absolutely  no  anaemia  or  other  variation  from 
the  normal. 3  The  appearance  of  the  skin  is  probably  due  to  the 
action  of  the  extreme  climate  on  the  peripheral  nerves  and 
vessels.  Tropical  anaemia  is  a  condition  not  of  the  blood,  but 
of  the  skin  and  subcutaneous  tissues. 

Every  one's  experience  includes  a  few  persons  who  are  per- 
fectly well  despite  an  almost  bloodless  condition  of  the  skin. 

On  the  other  hand,  anaemia  may  exist  where  there  is  a  good 
color  in  the  face. 

We  are  to  judge  of  anaemia,  then,  solely  by  the  blood  exam- 
ination, and  this  judgment  can  be  accurately  made  on  the  basis 
of  the  small  fraction  of  a  drop  used  for  examination,  provided 
always  that  our  technique  is  good,  and  provided  we  make  allow- 
ances for  a  considerable  error  wherever  there  is  reason  to  sup- 
pose that  any  venous  and  capillary  stasis  is  present,  or  that  the 
blood  is  temporarily  concentrated  or  diluted. 

Distinction  between  Primary  and  Secondary  Ancemia, 

In  one  sense  all  anaemia  is  secondary.  It  is  due  to  some 
cause,  a  symptom  in  a  chain  of  events.  But  in  some  cases  we 
know  the  cause  and  in  some  we  do  not. 

(a)  Primary  anaemia  is  that  in  which  the  causal  factors  are 

1  Boston  Medical  and  Surgical  Journal,  August  23d,  1894. 

2  Where  the  haemoglobin  is  high  the  number  of  corpuscles  is  never  con- 
siderably diminished. 

3  So  far  as  present  methods  of  examination  go. 


84  CLINICAL   BLOOD   EXAMINATION. 

either  entirely  unknown  or  are  apparently  insufficient  to  cause  so 
severe  a  disease.  This  division,  like  most  of  our  statements 
about  the  blood,  is  a  rough-and-ready  one,  held  to  provisionally 
until  a  better  classification  is  discovered.  It  has  a  certain  utility 
if  not  used  with  any  less  simple  meaning  than  that  given  above. 

In  view  of  our  ignorance  of  the  blood-making  functions,  there 
is  little  difference  between  saying  that  a  primary  anaemia  is  a 
disease  of  the  blood-making  organs  and  saying  that  it  is  one 
whose  cause  is  unknown,  especially  as  the  pathological  appear- 
ances in  the  bone  marrow  recorded  in  cases  of  so-called  primary 
anaemia  do  not  differ  from  those  which  can  be  brought  about 
experimentally  by  bleeding.  There  is  no  good  evidence  that 
there  are  any  primary  diseases  of  the  blood-making  functions. 
A  case  of  secondary  anaemia  is  one  in  which  we  have  an 
obvious  cause  such  as  hemorrhage  or  malaria  for  the  loss  of 
corpuscle  substance.  Eemove  the  cause  and  the  anaemia  ceases. 
Sometimes,  however,  after  removal  of  the  cause,  e.g.,  after 
cure  of  a  case  of  syphilis,  the  anaemia  set  agoing  by  the  syph- 
ilis persists.  On  the  other  hand,  there  are  few  patients  with 
"primary"  anaemia  who  cannot  recall  some  event  in  their  past 
lives  sufficient  to  account  for  a  certain  grade  of  ancemia  (e.g.,  a 
nervous  shock,  a  hemorrhage,  an  attack  of  tertian  malaria). 
Yet  if  the  anaemia  that  occurs  after  so  slight  a  cause  is  of  the 
pernicious  or  fatal  type,  we  may  fairly  call  it  "primary."  By 
this  we  mean  that  though  the  "  cause"  assigned  might  produce 
some  anaemia,  it  was  not  sufficient  to  produce  tliis  fatal  anaemia 
and  has  presumably  little  or  no  connection  with  it.  "Primary" 
means  not  the  absence  of  any  cause  of  anaemia  in  the  history, 
but  the  absence  of  any  sufficient  cause  so  far  as  is  known. 

An  attack  of  tertian  malaria  or  a  history  of  bleeding  piles  does- 
not  cause  fatal  anaemia  in  999  out  of  1,000  people  who  have  such 
a  history.  In  the  1000th  it  is  a  case  of  post  lioc  and  not  propter 
hoc.  Given  the  unknown  cause  that  does  lead  to  "  primary"  an- 
aemia, and  it  might  be  that  a  pregnancy,  a  nervous  shock,  or 
the  presence  of  intestinal  parasites  would  act  as  the  straw  that 
breaks  the  camel's  back;  but  the  important  causal  factor  is  the 
unknown  factor.  It  is,  then,  by  their  etiology  and  not  by  their 
symptoms  or  by  the  blood  examination  alone  that  we  distinguish 
primary  from  secondary  anaemia. 

It  is  true  that  in  the  majority  of  cases  we  can  tell  from  the 
blood  examination  alone  whether  a  case  is  without  known  cause. 


ANAEMIA   AND    HYDRJEMIA.  85 

(  =  "primary")  or  symptomatic  (=  "secondary").  But  there 
appear  to  be  enough  exceptions  to  this  rule  to  make  us  cautious 
about  stating  it  as  a  law. 

To  be  discussed    under 


Secondary.  VII. 

Secondary  Ancemia. 

I.  First  Stage.  —  I  denned  anaemia  above  as  a  diminution  in 
corpuscle  substance.     In  the  milder  types  of  this  condition  the 
number  of  red  corpuscles  is  not  diminished  at  all,  but  the  indi- 
vidual cell  is  small,  pale,  and  of  light  weight,  through  loss  of 
nitrogenous  matter.     This  is  appreciated  : 

(a)  As  a  lack  of  coloring  matter  ; 

(6)  As  a  lowering  of  the  specific  gravity. 

In  the  mildest  grades  of  secondary  anaemia  there  are  no 
further  changes.  Such  cases  are  those  due  to  errors  in  hygiene 
—bad  air,  poor  food,  lack  of  light  or  exercise  —  to  small  hem- 
orrhages, and  to  the  earlier  stages  of  the  diseases  next  to  be 
mentioned. 

The  lack  of  coloring  matter  is  usually  not  present  in  every 
cell,  as  is  seen  in  the  stained  specimens.  Some  are  very  pale  at 
the  centre,  while  others  are  well  stained. 

II.  Second  Stage.  —  Usually  the  next  changes  to  appear  are, 
like  those  already  mentioned,  qualitative,  the  number  of  red  cells 
still  remaining  normal  or  approximately  so. 

The  individual  cell  as  seen  in  fresh  preparations  is  more  or 
less  deformed  and  varies  from  its  normal  diameter,  dwarfed 
forms  usually  being  commoner  than  the  giant  forms.  These 
variations  in  size  and  shape  are  sometimes  termed  "  poikilocy- 
tosis,"  and  the  dwarf  and  gianL  forms  are  called  respectively 
microcytes  and  macrocytes. 

Maragliano  1  has  included  the  above  changes,  together  with 
others  about  to  be  described,  under  the  heading  of 

Necrobiosis  in  the  red  corpuscles,  attributing  them  to  a  patho- 
logical condition  of  the  serum. 

The  changes,  united  under  this  heading  may  be  divided  for 
convenience'  sake  into: 

(a)  Endoglobular  changes. 

1  XI.  Cong,  f  .  Inn.  Med.  ,  Leipzig,  1892. 


86 


CLINICAL  BLOOD   EXAMINATION. 


(b)  Poikylocytosis  and  crenation. 

(c)  Changes  in  staining  properties. 

(d)  Changes  involving  motility  in  the  corpuscle  as  a  whole, 
or  in  parts  of  it. 

(e)  Decrease  in  the  average  diameter  of  corpuscles  with  loss 
of  the  power  to  form  rouleaux. 

All  these  changes  may  be  watched  in  normal  blood  outside 
the  vessels,  as  necrosis  gradually  comes  on  from  contact  with  the 
air.  Under  pathological  conditions  the  same  changes  may 

occur  outside  the  body,  but 
more  quickly  than  usual 
(as  other  diseased  tissues 
decompose  more  quickly 
after  death  than  those  of 
a  sound  man  suddenly 
killed),  or  inside  the  body. 

(a)  Endoglobular  Changes 
(see  Fig.  27,  a).— These 
consist  in  the  appearance 
of  clear  hyaline  spaces  of 
various  shapes  within  the 
corpuscle,  round,  triangu- 
lar, rod-shaped,  etc.  In 
the  fresh  specimen  they 
change  their  shape  rapidly  and  continually;  in  dried  and 
stained  specimens  they  appear  as  sharply  outlined  light  spaces 
in  the  corpuscle.  In  normal  blood  these  changes  occur  after 
thirty  to  seventy  minutes  outside  the  vessels.  In  some  patho- 
logical conditions  specimens  show  them  the  instant  the  blood 
is  collected,  and  presumably  they  were  present  before  it  left  the 
vessels. 

(b)  Crenation   and  Poikilocytosi  s    (Fig.  27,   b). — What   we 
ordinarily  know  as  crenation  in  the  corpuscles  is  the  same  sort 
of  process  which,  occuring  within  the  vessels,  we  call  poikilocy- 
tosis.     A  lump  rises  at  one  or  more  points  in  the  corpuscle, 
becomes  more  pointed,  and  gradually  the  whole  cell  acquires 
amoeboid  motions,  assuming  in  succession  the  various  shapes 
with  which  we  are  familiar  in  poikylocytes. 

(c)  The  pointed  projections  may  break  off  and  move  about 
actively  in  the  plasma.     These  motions,  as  well  as  the  preceding 


FIG.  27.  —Degenerative  Changes  in  Bed  Cells. 


AND    HYDRJ3MIA. 


87 


amoeboid  movement  of  the  whole  corpuscle,  are  to  be  explained 
as  irregular  contractions  of  the  necrobiotic  protoplasm,  similar 
in  a  general  way  to  the  actions  of  a  hen  after  its  head  is  cut  off. 
These  motions  are  not  to  be  confounded  with  the  finer  Brownian 
molecular"  movement  to  be  seen  in  any  healthy  cell.  The 


or 


small  bits  broken  off  (Fig.  27,  c)  are  doubtless  the  dwarf  cells 
seen  in  dried  and  stained  preparations.  Curiously  enough, 
these  fragments  tend  again  to  assume  the  biconcavity  character- 
istic of  normal  cells,  as  a  drop  of  fat  breaks  into  smaller  but 
eimilar  drops. 


FIG.  28.— Elongated  or  Oval  Corpuscles  in  a  Case  of  Pernicious  Anaemia. 

(d)  Oval  Shape. — A  great  many  cases  of  pernicious  anaemia 
and  some  other  diseases  (see  Epidemic  Dropsy,  page  240)  show 
a  marked  tendency  to  oval  shapes  in  corpuscles  not  otherwise 
considerably  deformed.  Even  in  normal  blood  I  think  there 
are  a  small  number  of  oval  forms,  and  in  anaemia  this  number 
may  be  greatly  increased  till,  as  in  Fig.  28,  we  get  ,all  the  cells 
elongated.  The  same  appearance  can  be  produced  by  roughness 
in  spreading  the  blood,  but  in  such  case  the  deformed  corpuscles 
all  point  one  way. 


88  CLINICAL   BLOOD   EXAMINATION. 

(e)  Changes  in  Staining  Properties. — Normal  red  corpuscles 
have  affinity  only  for  acid  stains  (eosin).  The  same  degenera- 
tive changes  that  lead  to  the  alterations  in  shape  and  size  above 
described  alter  the  staining  properties  of  the  cell  as  well,  so 
that  it  takes  up  two  or  three  colors  (according  to  the  number 
present  in  the  stain) ,  either  as  a  diffuse  mixture  or  irregularly, 
some  parts  of  the  cell  taking  color  differently  from  others.  This 
has  been  termed  a  " polychromatophilic"  or  degenerative  change. 
Some  observers  have  supposed  it  to  be  rather  of  the  nature  of 
regeneration,  believing  that  the  cells  take  color  in  this  unortho- 
dox way  because  they  are  half -developed,  but  the  weight  of  evi- 
dence is  that  they  are  degenerative  changes. 

(/)  In  many  secondary  anaemias,  especially  in  those  asso- 
ciated with  inflammations,  the  average  diameter  of  the  cells  is 
lessened,  and  the  rouleaux  are  not  formed. ' 

( g )  Cells  may  lose  their  haemoglobin  altogether,  leaving 
only  the  shell  of  the  corpuscle  behind  (see  Fig.  27,  d). 

Now  all  these  necrobiotic  changes  are  characteristic  of  the 
severer  grades  of  secondary  anaemia  such  as  occur  in  cancerous 
cachexia,  phthisis,  nephritis,  etc. 

The  changes  of  staining  affinity  are  less  common  than  the 
others,  and  usually  represent  the  severest  grades  of  anaemia,  but 
they  have  also  been  noted  occasionally  in  smallpox,  measles, 
scarlet  fever,  typhus,  and  purpura. 

In  pernicious  anaemia  they  are,  as  a  rule,  much  more  common 
than  in  any  other  disease.  Maragliano  considers  these  degener- 
ative changes  to  be  due  to  toxic  plasma.  A  lessened  resistance 
to  the  ordinary  plasma-environment  on  the  part  of  the  red  cells 
would  also  explain  them,  and  in  such  affections  as  paroxysmal 
haemoglobinuria  it  seems  the  most  probable  cause.  In  syphilis 
the  abnormal  sensitiveness  of  the  red  cells  to  the  influence  of 
mercury  seems  another  instance  where  the  red  cells  are  imma- 
ture, decrepit,  or  weak.  In  syphilitic  children,  for  instance, 
mercury  easily  gives  anaemia,  while  in  healthy  children  it  does 
not.  This  will  be  discussed  more  fully  under  syphilis. 

The  necrobiotic  phenomena  above  described  have  been  ob- 
served by  Maragliano  in  carcinoma,  lead  poisoning,  leukaemia, 
pernicious  anaemia,  purpura,  cirrhotic  liver,  nephritis,  pneu- 

1  But  in  the  severest  forms  of  anaemia  the  diameters  are  apt  to  be  in- 
creased (see  below,  Pernicious  Anaemia). 


ANAEMIA   AND    HYDRJEMIA.  89 

monia,  malaria,  typhoid,  erysipelas,  and  tuberculosis.  Celli 
and  Guarnieri  (Fortschritte  der  Medicin,  1889,  No.  14)  found 
them  in  measles  and  scarlet  fever.  Weintraub  (Virchow's  Ar- 
chiv,  Vol.  131)  noted  them  in  epilepsy,  pyaemia,  and  catarrhal 
jaundice. 

A  decreased  resistance  to  pressure  of  electric  currents  and 
other  influences  has  also  been  noted  by  v.  Limbeck  in  some 
cases. 

Such  weakening  of  the  red  cells  experimentally  produced  in 
animals  by  poisons  has  been  found  (Mya  and  Sanarelli,  Arch, 
ital.  di  Biolog.,  XVII.,  1892)  to  increase  the  susceptibility  to 
infectious  diseases. 

III.  Third  Stage. — Here  the  number  as  well  as  the  quality 
of  the  red  cells  begins  to  suffer.     So  far  I  have  mentioned  only 
the  qualitative  changes  in  secondary  anaemia  and  have  purposely 
made  these  changes  more  prominent  than  the  actual  diminution 
in  the  count  of  red  cells,  because  it  is  only  comparatively  rarely 
and  in  very  marked  cases  that  the  diminution  in  red  corpuscles 
is  considerable.     The  blood  characteristic  of  most  cases  of  sec- 
ondary anaemia  is  one  in  which  the  number  of  red  cells  is  ap- 
proximately normal. 

The  important  exceptions  to  this  rule  are:  1.  The  anaemias 
of  infancy  and  early  childhood.  2.  Large  hemorrhages  (soon 
after  their  occurrence).  3.  Malaria.  4.  Acute  septicaemia. 

The  direct  and  rapid  destruction  of  the  corpuscles  by  the 
malarial  organism  or  hemorrhage  account  for  this.  Of  sepsis 
and  the  anaemias  of  infancy  we  shall  speak  later. 

IV.  Fourth  Stage. — The  blood  of  secondary  anaemia  shows 
often  evidence  not  only  of  degeneration  and  destruction  of  the 
cells  but  also  of  regenerative  changes,  namely : 

Nucleated  Red  Cells. 

These  are  usually  divided  into  three  groups 
(a)  Normoblasts. 
(&)  Megaloblasts. 
(c)  Microblasts. 

Normoblasts. 

(a)  The  first  are  normally  present  in  moderate  number  in  the 
bone  marrow  of  healthy  persons,  and  in  great  numbers  in  the 


90  CLINICAL   BLOOD    EXAMINATION. 

marrow  after  hemorrhage.  They  are  generally  considered  to  be 
a  younger  stage  in  the  life  of  the  corpuscle  than  the  non- 
nucleated  forms  seen  in  the  circulating  blood.  Hence  the  ap- 
pearance in  the  peripheral  circulation  of  this  form  of  nucleated 
cell  is  considered  to  mean  that,  in  the  comparatively  plentiful 
reproduction  of  red  cells  called  forth  in  the  marrow  by  the 
anaemia,  a  certain  number  of  red  cells  leave  the  nursery  (the 
marrow)  before  they  are  grown  up  and  circulate  for  a  time  in 
their  immature  state.  A  normoblast,  then,  represents  an  im- 
mature red  corpuscle  (see  Plate  IV.). 

In  size  and  color  it  is  like  an  ordinary  red  cell  except  that  we 
find,  usually  somewhat  to  one  side  of  it,  a  round  nucleus  about 
one-half  the  diameter  of  the  whole  cell.  With  Ehrlich's  tricolor 
mixture,  this  nucleus  stains  very  deep  blue,  nearly  black,  and  is 
sharply  outlined  against  the  pale  yellow  of  the  cell  body  around 
it. 

The  cell  often  looks  as  if  it  were  pushing  its  nucleus  out, 
i.e.,  in  many  instances  we  see  the  nucleus  projecting  over  the 
edge  of  the  corpuscle,  or  half  out  of  it,  and  occasionally  we  find 
it  lying  beside  the  corpuscle  from  which  it  has  just  emerged; 
but  this  appearance  is  probably  an  artefact  and  not,  as  Ehiiich 
thought,  the  regular  way  of  disposing  of  the  normoblast  nucleus. 

Very  frequently  the  nucleus  has  toward  the  centre  a  light 
spot,  sometimes  so  brilliant  that  it  looks  like  the  reflection  of 
light  from  the  surface  of  a  drop  of  ink  or  any  dark  liquid,  what 
artists  call  the  "high  light."  Occasionally  there  are  several  of 
these  light  spots  in  a  nucleus,  or  it  may  be  all  light  blue-gray  ex- 
cept a  dark  blue  rim.  This  is  the  commonest  type  of  normo- 
blast. But  now  and  then  we  meet  with  one  when  the  nucleus 
is  more  or  less  separated  into  two  or  more  pieces.  These  pieces 
are  usually  connected  by  pale-staining  "bridges,"  perhaps  ra- 
diating from  a  centre  so  that  the  nucleus  is  "rosette-shaped," 
or  it  may  take  any  one  of  a  large  number  of  different  shapes. 
The  parts  of  the  nucleus  which  are  nearest  the  periphery  of  the 
cell  usually  stain  deeper  than  the  "  bridges"  which  join  them. 

Sometimes  the  nucleus  breaks  apart  completely  and  we  find 
two  or  more  separate  unconnected  nuclei  within  the  single  cell.1 
Or  one  of  the  pieces  may  be  outside  the  cell  and  the  others  inside. 

1  Apparent^  the  nucleus  is  absorbed  or  degenerates  (see  Israel  and  Pap- 
penheim  :  Virchow's  Archiv,  vol.  143). 


ANEMIA    AND    HYDR^MIA.  91 

Barest  of  all  is  the  appearance  of  true  mitosis  in  the  nucleus 
of  a  normoblast. 

Megaloblasts. 

(b)  The  typical  megaloblast  as  usually  described  is  so  unlike 
the  normoblast  that  we  should  not  naturally  think  of  them  as 
near  relations. 

It  does  not  occur  anywhere  in  the  healthy  adult  body,  not 
even  in  the  bone  marrow.  In  the  early  foetal  marrow  and  in 
the  marrow  and  circulating  blood  of  grave  forms  of  anaemia  it  is 
to  be  found,  usually  in  company  with  a  certain  number  of  nor- 
moblasts. 

Ehrlich  described  megaloblasts  as  the  sign  or  product  of 
a  different  type  of  blood  formation,  namely,  the  foetal  type, 
and  considered  those  anaemias  in  which  it  occurs  as  tend- 
ing to  a  return  of  the  blood  to  the  foetal  state.  [This  has 
been  recently  confirmed  by  the  researches  of  Pappenheim, 
though  Ehrlich 's  detailed  theory  of  two  methods  of  blood 
formation  is  now  generally  discredited.  All  nucleated  red 
cells  lose  their  nuclei  by  "absorption";  none  by  extrusion.] 
Ehrlich  regarded  the  presence  of  megaloblasts  as  a  bad  prog- 
nostic sign,  and  believed  that  a  pernicious  or  fatal  anaemia  was 
characterized  by  an  excess  of  these  cells  over  the  normoblasts. 
He  recognized  that  they  might  be  found  in  various  milder 
forms  of  anaemia;  but  here  the  prevailing  type  is  the  normo- 
blast, and  regeneration  may  be  more  active  than  degenera- 
tion. In  his  general  conception  of  the  prognostic  import  of 
megaloblasts  Ehrlich  has  been  supported  by  the  weight  of 
later  clinical  observation,  although  it  has  been  shown  that  the 
anaemia  due  to  intestinal  parasites  can  be  cured,  despite  the 
presence  of  the  megaloblasts  as  the  prevailing  type  of  nucleated 
red  cells.  So  far  as  I  know  this  is  the  only  exception  to 
Ehrlich 's  rule. 

The  typical  megaloblast  is  an  abnormally  large  cell  (11  to  20  ,a 
in  diameter,  frequently  showing  marks  of  degeneration  (poly- 
chromatophilia)  in  its  protoplasm,  which  is  therefore  brownish 
or  purplish  with  the  Ehrlich-Biondi  stain.  Its  nucleus  is  very 
large,  filling  most  of  the  cell,  and  contrasts  with  the  normoblast 
nucleus  not  only  by  its  greater  size  but  by  the  pale,  even  stain 
which  it  takes  up.  The  commonest  color  of  the  nucleus  with 


92  CLINICAL  BLOOD   EXAMINATION. 

the  Ehrlich-Biondi  stain  is  pale  green  or  robin 's-egg  color. 
It  is  not  stained  evenly  but  dotted  over  with  purplish  granules 
arranged  in  a  fine  mesh  like  the  knots  in  a  fish-net  (see  Plate  IV.). 

Outside  the  nucleus  there  is  usually  a  narrow  band  of  clear 
white,  apparently  an  empty  space,  separating  the  nucleus  from 
the  encircling  protoplasm.  The  protoplasm  close  round  this 
colorless  ring  is  usually  stained  more  deeply  than  the  rest  of  the 
cell.  Cracks  and  "  flaws"  are  sometimes  to  be  seen  in  the  proto- 
plasm, giving  evidence,  as  its  purplish  stain  does,  of  the  necro- 
biotic  changes  described  by  Maragliano. 

The  outline  of  the  whole  may  be  quite  circular :  oftener  it  is 
oval  or  somewhat  irregular,  but  rarely  much  deformed. 

Microblasts. 

(c)  Microblasts,  which  are  rarer  than  either  of  the  varieties 
just  described,  consist  of  a  nucleus  like  that  of  a  normoblast  or 
smaller,  and  contained  in  a  cell  body  smaller  than  the  normal 
red  corpuscle.  In  the  writer's  experience  the  cell  body  is  usu- 
ally reduced  to  a  few  shreds  of  discolored  protoplasm  hanging 
about  the  nucleus  (see  Plate  IV.).  Their  clinical  significance 
is  usually  supposed  to  be  that  of  megaloblasts. 


"Atypical  Forms." 

As  a  rule  we  find  in  a  given  specimen  of  blood  only  typical 
normoblasts,  microblasts,  or  megaloblasts,  and  accordingly  can 
easily  reckon  up  the  number  of  each  kind  and  see  which  type  of 
blood  formation  predominates.  Sometimes  there  are  a  few  cells 
present,  about  the  classification  of  which  we  cannot  come  to  a 
decision,  and  I  have  occasionally  seen  a  specimen  of  blood  con- 
taining a  large  number  of  nucleated  red  cells  no  one  of  ivhicli 
could  strictly  be  classed  either  as  a  "normoblast,"  a  "megalo- 
blast,"  or  a  "  microblast, "  as  these  are  defined  above. 

The  researches  of  Pappenheim  have  thrown  much  light  on 
this  difficulty.  While  insisting  with  Ehrlich  that  the  megalo- 
blast  and  the  normoblast  represent  respectively  the  early  fostal 
and  the  post-uterine  types  of  blood  formation,  and  that  there 
are  no  real  "transitions"  from  the  one  to  the  other,  he  yet 
recognizes  that  the  two  varieties  are  not  absolutely  to  be  differ- 
entiated by  any  of  the  ordinarily  accepted  criteria  such  as  size, 


Examination  of  the  Blood. 


PLATE  IV. 


Normal  red  cells 


m 


' 


ifii 


Normoblasts 


Microblast 


Cells  in  karyo- 
-  ->     kinesis 


M 
f 

i 


mo 

;. 


Varieties  of  Nucleated  Red  Cells. 

m.  m.  m.  m.  =  Typical  megaloblasts.    D.  D.  D.  D.  =  Cells  with  dividing  nuclei, 
o.  o.  o.  o.  o.  o.  o.  =  Other  (unnamed)  varieties  of  nucleated  red  corpuscles. 


Scale  of  u 


.'  Polychromatophilis  cells 
CeUs  deformed  in  size  or  shape. 


K.  C.  Gabot  fee. 


Lith.  An«t.  v.  K.  A..  Funka,  Leipzig. 


PLATE  IV. 

(1 )  m,m,m,  m —  Young  megaloblasts. 

(2)  D,D,D,D;  the  upper  two  are  probably  old   normoblasts  with  de- 
generating nuclei,  and  the  lower  two  old  megaloblasts  with  nuclei  is  a 
similar  condition. 

(3)  0,0,0,0,  etc. — The  two   cells  in  the  lower  right-hand  corner  are 
probably  old  megaloblasts  whose  nuclei  are  nearly  absorbed.     The  three 
cells  immediately  to  the  left  of  these  are  probably  young  normoblasts— the 
lowest  one  being  the  youngest.     The  other  four  cells  marked  "0,0,0,0" 
(those  to  the  extreme  left)  are  probably  middle-aged  megaloblasts.     The 
two  labelled  "  Normoblasts"  are  really  old  normoblasts.     The  appearance 
of  extrusion  of  the  nucleus  on  one  of  them  is  probably  an  artefact.     The 
large  cell  on  the  extreme  upper  right-hand  corner  is  probably  a  megalo- 
blast  with  a  "  pyknotic"  or  oedematous  (degenerating)  nucleus. 

(4)  In  the  young  or  "typical"  megaloblasts  (m,m,m,m)  note  the  white 
line  around  the  nucleus,  the  variations  in  its  tint,  and,  in  two  of  them, 
the  discolorations  of  the  protoplasm  (polychromatophilia),  especially  near 
the  nucleus.     The  lower  of  the  two  cells  in  karyokinesis  shows  this  best. 

(5)  In  the  microblast  note  the  ragged  edge  of  the  protoplasm. 

(6)  In  the  lower  portion  of  the  plate  ("cells  deformed  in  size  or  shape") 
an  actual  field  from  a  case  of  pernicious  anaemia  was  copied.     Macrocytes 
(or  large  cells) ,  microcytes  (or  small  cells) ,  and  m  isshapen  cells  or  poiki- 
locytes  are  shown. 

(7)  The  " polychromatophilic  cells"  in  the  lower  right-hand  corner  were 
stained  with  the  same  mixture  as  those  to  the  left  of  them,  but  have  taken 
up  other  colors  besides  the  orange  G,  which  alone  is  taken  up  by  normal 
red  cells. 


ANAEMIA   AND    HYDRJEMIA.  93 

color  of  nucleus,  etc.  Most  "  megaloblasts, "  he  admits,  are 
larger  than  most  normoblasts,  but  there  are  occasional  giant  nor- 
moblasts  and  dwarf  megaloblasts  which  by  size  alone  are  indis- 
tinguishable. The  large,  pale,  delicately  netted  nucleus  of  the 
"megaloblasts"  is  simply  a  young  nucleus.  All  young  nuclei 
are  relatively  large  and  pale,  while  the  small  dark  nucleus  of 
the  normoblast  is  simply  an  old  or  degenerating  nucleus.  The 
real  criteria  of  the  two  varieties,  according  to  Pappenheim,  is 
not  the  size  or  color  of  nucleus  nor  of  the  whole  cell,  but  the 
structure  of  the  nuclear  network.  This  is  a  point  difficult  to 
make  out  by  ordinary  staining  methods  and  not  easily  appre- 
ciated. Luckily  for  us,  most  "megaloblasts"  are  larger  than 
most  "  normoblasts ;"  and  further,  most  of  them  as  seen  in  the 
blood  are  young  (i.e.,  have  large  pale  nuclei  with  delicate  chro- 
matin  network),  while  most  "normoblasts"  are  old,  as  shown  by 
their  small,  dark,  coarse-skeined  nucleus,  so  that  in  the  majority 
of  cases  Ehrlich's  criteria  for  the  two  varieties  are  sufficiently 
correct  for  diagnostic  purposes.  Pappenheim  of  course  wishes 
to  abandon  the  terms  " megaloblast"  and  "normoblast"  alto- 
gether, but  since  size  still  remains  the  most  easily  recognized 
criterion  of  "  megaloblasts"  and  "  normoblasts"  I  shall  continue 
to  use  the  terms.  On  the  chances,  then,  any  nucleated  red  cell 
over  10  ;j.  diameter  should  be  classed  as  a  megaloblast  ivhatever  the 
appearance  of  its  nucleus,  and  any  nucleated  red  cell  under  10  v- 
diameter  is  probably  a  normoblast  whatever  the  appearance  of  its 
nucleus.  Microblasts  simply  represent  degenerating  forms 
(usually  normoblasts)  whose  protoplasm  is  falling  away.  The 
clinical  significance  of  the  two  varieties  is  just  such  as  Ehrlich 
supposed.  [These  points  will  be  made  clearer  by  reference  to 
Plate  IV.  and  the  remarks  intended  to  explain  it.] 

In  most  cases  of  severe  secondary  anaemia  we  find  a  few 
normoblasts.  In  very  severe  forms,  whatever  the  cause,  we  may 
or  may  not  find  an  occasional  megaloblast.  But  these  are 
much  rarer  than  the  normoblasts,  even  in  the  severest  types  of 
secondary  anaemia.  The  only  exceptions  to  this  rule  are  the 
anaemias  due  to  intestinal  parasites,  in  which,  though  secondary 
and  curable,  the  megaloblasts  in  some  cases  predominate  over 
the  normoblasts. 

Summing    up    the    changes    characteristic     of    secondary 


94 


CLINICAL   BLOOD    EXAMINATION. 


anaemia,  which  includes  almost  all  the  important  pathological 
appearances  occurring  in  red  cells,  we  have : 


I. 


(  (a)  Lack  of  haemoglobin.  } 


specifics  Characteristic  of  mild  cases. 


TIT 

' 


(b)  Lowered 

(  gravity.  ) 

II.  The  above  and  necrobiotic )  Characteristic  of  moderate 
changes  of  Maragliano.      j  cases. 

(a)  Lack  of  red  cells.  ~1 

(b)  Presence     of     normo-  [Characteristic    of   severe 

blasts  and  the  above  [  cases. 

(I.  and  II.). 

IV.  Megaloblasts  and  the  above  )  Characteristic1* of  very  se- 
(I.,  II.,  and  III.).        )  vere  cases. 

The  changes  in  the  white  cells  will  be  discussed  in  the  next 
chapter. 

Among  the  commonest  causes  of  secondary  anaemia  are :  I. 
Infective  and  febrile  diseases,  acute  or  chronic.  II.  Malignant 
disease.  III.  Chronic  suppurations,  nephritis,  chronic  dysen- 
tery, cirrhosis  of  the  liver.  IV.  Bad  hygiene,  pregnancy,  and 
lactation.  V.  Intestinal  parasites.  VI.  Poisons  (lead,  arsenic, 
etc.). 

To  discuss  the  way  in  which  each  of  these  influences  acts 
in  producing  anaemia  is  tempting,  but  falls  outside  the  plan  of 
this  book. 

The  following  are  good  examples  of  the  condition  of  the 
blood : 

SECONDARY  ANJEMIA. 


o 

1 

1 

Red  cells. 

White 
cells. 

Per  cent, 
haemo- 
globin. 

Remarks. 

1 

23 

F. 

1,656,000 
2,048,000 
1,808,000 
1,568,000 
4,248,000 

2,300 
2,600 
3,200 
1,300 
2,300 

18 
24 
30 
58 
60 
72 

Post-malarial. 
After    7  days'  treatment. 
"    14      " 

«    24      «            " 

"    34      "            " 
"    43      "            " 

9, 

45 

M 

2,208,000 

50 

Post-malarial 

3 

4 

5 
6 

9 
41 

32 

40 

F. 
F. 

F. 
M. 

2,186,000 
3,240,000 

2,920,000 
2,040,000 

8,500 
5,400 

12,  000 
9,600 

30 
59 

47 
10 

Post-hemorrhagic  (8  hours)  . 
Post-hemorrhagic  (bleeding 
fibroid). 
After  abortion  with  hemorrhage. 
Chronic  dysentery. 

Differential  count  in  case  6  showed  polynuclear  cells,  66. 3 ;  myelo- 
cytes,  1.4;  8  normoblasts,  5  megaloblasts — seen  in  counting  400  leuco- 
cytes. 


ANAEMIA   AND    HYDR^MIA.  95 


2.  HYDB^MIA. 

(a)  Seen  from  the  opposite  point  of  view  almost  all  cases  of 
anaemia  are  hydraemic.  That  is,  if  the  total  volume  of  blood  is 
to  remain  approximately  constant  (as  it  appears  to  do) ,  any  loss 
of  solids  (corpuscle  substance)  must  be  made  up  by  water  taken 
in  from  the  tissues.  Hence  any  anaemic  person's  blood  is  thin, 
watery,  or  hydraemic.  Women's  blood  is  somewhat  more 
hydraemic  than  men's,  because  less  rich  in  cells.  Ordinary 
chlorosis  and  secondary  anaemia  show  no  more  water  than 
normal  in  the  serum,  but  the  cells  are  probably  somewhat  water- 
logged. 

(6)  In  many  conditions  of  dropsy,  whether  from  heart  or 
kidney,  we  may  have  more  water  than  normal,  both  in  the 
plasma  and  in  the  corpuscles  themselves,  which  are  capable 
of  taking  up  considerably  more  than  their  normal  amount  of 
water. 

(c)  Any  temporary  dilution  of  the  blood  under  the  conditions 
mentioned  above  (ingestion  of  liquid,  lowered  blood  pressure, 
etc.)  is  from  one  point  of  view  a  hydj-aemic  condition. 

No  special  clinical  significance  attaches  to  it  other  than  that 
of  anaemia,  whose  correlative  it  is. 


CHAPTEK  YIII. 

LEUCOCYTOSIS— LYMPHOCYTOSIS—EOSINOPHILIA— 
MYELOCYTES. 

MUCH  confusion  Las  been  caused  in  the  past  by  the  failure 
to  see  in  leuksemic  blood  anything  more  than  an  extreme  and 
permanent  form  of  leucocytosis,  while  leucocytosis  was  thought 
of  as  a  mild  and  temporary  leukaemia. 

We  know  now  that  they  are  totally  different  phenomena, 
differing  not  in  the  number,  but  in  the  kind  of  cells  present  in 
the  increased  numbers. 

Definition. 

There  are  many  difficulties  in  denning  leucocytosis.  To  my 
mind  the  term  is  best  used  to  mean :  An  increase  in  the  number 
of  leucocytes  in  the  peripheral  blood  over  the  number  normal  in  the 
individual  case,  this  increase  never  involving  a  diminution  in  the 
polymorphoniiclear  varieties,  but  generally  a  marked  absolute  and 
relative  gain  over  the  number  previously  present. 

(a)  I  say   "in   the  peripheral   blood"  because  certain    ob- 
servers  hold  that  leucocytosis  is  not  a  real   increase  in  the 
total  number  of  leucocytes  in  the  blood,   but  only  an  affair 
of  distribution,  the  cells  being  drawn  or  attracted  to  the  pe- 
riphery and  out  of  the  internal  organs.     Whether  this  theory 
be  true  or  not,  it  is  accurate  to  say  that  in  the  drop  which  we 
draw  (whether  also  in  the  internal  organs  or  not),  the  leuco- 
cytes are  present  in  increased  numbers  per  cubic  millimetre. 

(b)  In  persons  not  usually  to  be  considered  sick,  but  simply 
somewhat  wizened  or  ill-nourished,  the  normal  count  of  white 
cells  may  be  as  low  as  three  thousand  per  cubic  millimetre. 
For  such  an  individual  ten  thousand  cells  per  cubic  millimetre 
would  be  a  decidedly  pathological  condition.     On  the  other 
hand,  there  are  persons,   usually  those  of  notable  vigor  and 
good  nutrition,  whose  white  cells  rarely  fall  below  ten  thousand. 

Obviously  we  must  take  account  of  these  differences  both  in 
our  definition  and  in  our  practice  if  we  are  to  reason  correctly 
from  the  data  of  blood  examination. 


LEUCOCYTOSIS.  97 

(c)  Further  we  must  lay  stress  upon  the  varieties  of  leuco- 
cytes whose  increase  constitutes  leucocytosis  in  distinction  from 
either  variety  of  leukaemia  (splenic-myelogenous,  or  lymphatic). 

For  instance,  given  a  count  of  eighty  thousand  leucocytes 
per  cubic  millimetre,  we  cannot  tell  without  knowing  the  va- 
rieties of  cells  present  whether  the  case  is  a  genuine  leukaemia 
or  a  merely  leucocytosis  symptomatic  of  pneumonia,  suppura- 
tion, malignant  disease,  or  other  conditions. 

(d)  Thus  defined  leucocytosis  is  of  two  kinds.     1.  That  in 
which  the  relative  proportions  of  the  different  varieties  to  each 
other  is  unchanged.     2.    That  in  which  the  increase  is  made  up 
solely  or  largely  by  a  gain  in  the  polymorphonuclear  leucocytes. 

The  latter  includes  nearly  all  pathological  leucocytoses,  the 
former  being  confined  chiefly  to  the  physiological  leucocytoses 
next  to  be  described. 

(e)  Lastly,  in  order  to  be  sure  that  the  polymorphonuclear 
cells  are  not  decreased,  we  must  know  what  the  normal  percent- 
age/or that  individual  is.     The  normal  percentage  of  these  cells 
in  infancy  is  from  twenty-eight  to  forty  per  cent.     In  adults  it 
is  much  higher,  but  varies  like  the  total  count,  according  to 
conditions  of  nutrition,    etc.     Thus  the  normal  for  adults  is 
usually  set  at  from  sixty  to  seventy  per  cent,  but  no  one  indi- 
vidual's  blood   shows    such    variations    in  health,    and  if  we 
include  the  obviously  ill-nourished,  but  not  actually  sick,  and 
also  those  in  blooming  health,  we  shall  have  to  widen  our  nor- 
mal limits  considerably.     From   fifty  to   seventy-five  per  cent 
are  within  normal  limits  according  to  the  above  conception. 
But  obviously  we  can  make  no  absolute  judgment  by  a  standard 
so  vague.     It  is  much  better,  I  think,  to  consider  each  indi- 
vidual as  his  own  standard  within  these  limits,  his  count  of 
polymorphonuclear  cells  being  a  fair  measure  of  the  soundness 
and  vigor  of  his  metabolism.     Thus,  in  an  obviously  debilitated 
individual,  we  should  consider  seventy-two  per  cent  of  these 
cells  very  high,  while  in  a  vigorous  athlete  it  might  not  be  so. 

It  is  the  endeavor  to  include  all  these  limiting  conditions 
that  has  made  my  definition  so  long  and  involved.  It  gives  us, 
if  it  turns  out  to  be  true,  some  better  way  of  classing  individuals 
than  as  "sick"  or  "well"  as  regards  their  blood  state.  We  find 
out  how  well  or  how  sick  their  blood  is  (to  a  certain  extent) ,  (a) 

7 


98  CLINICAL   BLOOD   EXAMINATION. 

by  the  total  number  of  leucocytes  present,  and  (b)  by  the  pro- 
portion of  polymorphonuclear  neutrophiles  in  a  given  one  thou- 
sand of  these  leucocytes.  These  data  tell  us  approximately  hoiv 
normal  or  hoia  abnormal  a  given  individual's  blood  is.  When  a 
given  disease  like  pneumonia  occurs,  we  need  to  know,  if  pos- 
sible, what  is  the  ordinary  leucocyte  count  and  differential  count 
of  that  case,  on  top  of  which  a  leucocy  tosis  may  (or  may  not)  be 
built  up. 

Condition  of  stasis,  temporary  blood  concentration,  dilution, 
and  vasomotor  disturbances  must,  of  course,  be  excluded  or 
allowed  for,  since  these  may  increase  not  only  the  total  leu- 
cocyte count,  but  often  the  percentage  of  polymorphonuclear 
cells.  Whether  or  not  differences  of  race  make  any  difference 
in  the  normal  count  of  white  cells,  I  cannot  say,  but  certainly 
the  average  of  a  group  of  college  athletes  would  be  higher  than 
that  of  some  country  towns  in  New  England  where  everybody  is 
more  or  less  under-nourished ;  and  if  one  is  to  practise  among 
all  sorts  and  conditions  of  men,  I  think  he  cannot  but  expect  to 
find  people's  leucocytes  vary  all  the  way  from  3,000  to  10,500 
per  cubic  millimetre,  without  there  being  more  than  malnutrition 
to  account  for  the  lower  figures. 

Into  the  theories  of  how  leucocytosis  is  brought  about  I 
shall  not  enter ;  no  one  of  them  as  yet  commands  general  assent. 

"We  may  divide  leucocytoses  for  convenience'  sake  into :  1. 
Physiological  leucocytoses.  2.  Pathological  leucocytoses. 

PHYSIOLOGICAL  LEUCOCYTOSES. 

1.  Leucocytosis  of  the  new-born. 

2.  Leucocytosis  of  digestion. 

3.  Leucocytosis  of  pregnancy. 

4.  Leucocytosis  post-partum. 

5.  Leucocytosis  after  violent  exercise,  massage,  and  cold 
baths. 

6.  Leucocytosis  of  the  moribund  state. 

The  Leucocytosis  as  Affected  by  Digestion. 

(a)  Total  abstinence  from  food  lowers  the  leucocyte  count. 
In  the  blood  of  the  professional  faster  Succi,  the  number  sank 
within  his  first  week's  fast  to  861  per  cubic  millimetre.  After 


LEUCOCYTOSIS.  99 

the  first  week  it  rose  to  1,530,  and  remained  there  throughout 
his  thirty  days'  abstinence  (Luciani ').  The  polymorphonu- 
clear  cells  and  eosinophiles  are  said  by  Tauszk  to  be  increased 
in  chronic  starvation. 

Yon  Limbeck  counted  the  blood  of  a  melancholic  patient 
who  had  fasted  a  week,  and  found  2,800  white  cells  per  cubic 
millimetre.  These  facts  support  the  idea  that  the  number  of 
leucocytes  depends  (within  certain  limits)  on  the  individual's 
assimilation  of  food.  In  cancer  of  the  gullet  we  find  similar 
low  figures. 

(b)  After  a  meal  rich  in  proteids  the  leucocyte  count  rises 
about  thirty-three  per  cent  in  most  sound  persons.  Ten  thou- 
sand cells  may  perhaps  be  considered  the  average,  three  to  four 
hours  after  a  proteid  meal,  but  if  the  count  before  a  meal  is 
only  4,000  or  5,000,  digestion  will  perhaps  not  raise  it  above 
7,000,  while  vigorous  adults  may  show  13,000.  Digestion  leu- 
cocytosis  is  always  relative  to  the  count  of  the  individual's 
blood  when  fasting.  This  is  to  be  obtained  preferably  before 
breakfast,  as  during  the  day  the  leucocy  tosis  caused  by  one  meal 
may  not  be  gone  before  the  influence  of  the  next  meal  begins. 

Occasionally  we  see  sound  persons  with  little  or  no  digestive 
leucocytosis.  Some  of  these  cases  are  to  be  explained  by  habit- 
ual constipation  (v.  Limbeck) ;  in  others  the  reason  is  more 
obscure.  But  there  is  no  doubt  of  its  being  the  rule  after 
meals  of  mixed  or  proteid  diet.  In  herbivorous  animals,  and 
presumably  in  vegetarians,  it  is  not  found. 

Any  disease  of  the  gastro-intestinal  tract,  whether  functional 
or  organic,  may  prevent  the  appearance  of  the  digestion  leuco- 
cytosis (see  later  under  Diseases  of  the  stomach,  page  280).  In 
anaemic  and  debilitated  conditions  it  is  frequently  absent. 

In  children  it  is  especially  marked.  Schiff 2  records  a  case 
of  a  healthy  infant  whose  blood  an  hour  after  birth  showed 
19,500  (see  next  section),  after  its  first  meal  27,625,  and  after  its 
fourth  meal  36,000  white  cells  per  cubic  millimetre.  After  the 
second  day  this  gradually  diminished. 

Food  seems  to  call  forth  a  greater  leucocytosis  in  proportion 
as  it  is  a  novelty  in  the  stomach.  Cases  of  gastric  ulcer  who 
had  been  fed  exclusively  by  rectum  for  some  weeks  show  a 

1  "Des  Hungern,"  German  translation  by  O.  Frankel.     Hamburg,  1890. 

2Zeit.  f.  Heilk.,  xi.,  1890. 


100  CLINICAL   BLOOD    EXAMINATION. 

greater  leucocytosis  after  their  first  meal  than  later.  Perhaps 
the  size  of  the  digestion  leucocytosis  in  the  new-born  is  to  be 
similarly  explained.  In  diabetics  the  digestion  leucocytosis  is 
sometimes  very  large. 

The  leucocytosis  can  usually  be  observed  one  hour  after  a 
meal,  increases  for  two,  three,  or  even  five  hours  according  to 
the  slowness  of  digestion,  then  falls  again. 

Burian  and  Schur  '  found  an  increase  of  the  polymorpho- 
nuclear  varieties  in  those  cases  in  which  an  increase  of  the  total 
count  took  place  at  all.  Eosinophiles  show  no  regular  changes. 

Diagnostic  Value. 

1.  When  we  wish  to  know  whether  a  person  is  accurate  in  such 
statements  as  that  they  have  "eaten  nothing  for  a  week,"  we  can 
get  evidence  from  the  leucocyte  count,  which  should  be  very  low 
if  the   assertion  be  true.     Whenever  we  cannot  communicate 
with  a  patient  and  wish  to  know  how  much  food  he  has  taken  of 
late,  we  can  form  some  idea  from  the  blood  examination.     In 
the  case  of  a  patient  who  spoke  only  Russian,  I  was  led  to 
look  for  a  stenosis  of  the  gullet  by  the  lowness  of  the  leucocyte 
count  (2,700),  and  the  probang  confirmed  the  suspicion. 

2.  As  suggested  above,  we  can  form  some  idea  of  a  person's 
general  vigor,  nutrition,  and  capacity  to  assimilate  food  by  the 
number  of    leucocytes    and    the    proportion    of  mononuclear 
cells,   as  compared  with  the  average  figures  for  that  age  and 
locality.      Persons    debilitated  from    any   reason    are    apt    to 
show  it  in  their  blood  by  the  changes  above  mentioned,  the 
element  of  hysteria  being  sometimes   recognizable   by   other 
signs  (see  below:  " Eosinophilia, "  page  116). 

3.  Slowness  of  digestion  is  indicated  by  a  late  appearance  of 
the  digestion  leucocytosis.    The  inferences  to  be  drawn  from  the 
blood  in  diseases  of  the  gastro-intestinal  tract  will  be  discussed 
later  (page  274). 

4.  Perhaps  the  chief  importance  of  digestion  leucocytosis  is 
as  a  possible  cause  of  false  inferences,  through  being  taken  for  a 
pathological  increase.     Bearing  this  in  mind,  we  must  always 
examine  the  blood  as  near  a  meal  as  possible,  or  better  still 
before  breakfast. 

'Wien.  klin.  Woch.,  February  llth,  1897. 


LEUCOCYTOSIS. 


101 


Leucocytosis  of  the  New-Born. 

The  following  table  is  compiled  from  the  best  authorities  on 
the  subject  (Schiff,  Gundobin,  Bayer,  Hayem,  and  others) : 


Age. 

Bed  cells. 

Leucocytes. 

At  birth  

5  900  000 

17  000  to  21,000(26,- 

End  of  first  day 

7  000  000  to  8  800  000 

000  to  36,  000  after 
first  feeding)  . 
24  000 

"     second  day 

Generally  increased. 

30  000 

"     fourth  day  .       

6,  000,  000 

20,  000 

"     seventh  day  

5,000,000 

15,000 

Tenth  day 

10  000  to  14  000 

Twelfth  to  eighteenth  day  .  .  . 

12,000 

Sixth  month 

12,000 

Sixth  year  and  upward  

7,500 

The  increase  is  explained  by  Lepine,  v.  Limbeck,  and  others 
as  a  combination  of  blood  concentration  with  large  digestion 
leucocytosis.  Gundobin  and  others  are  opposed  to  this  theory. 
Certainly  the  influence  of  digestion  on  infant's  blood  is  much 
greater  than  in  adults.  After  a  meal  30,000  leucocytes  is  never 
a  very  high  count  in  infants  under  two  years. 

A  fuller  discussion  of  the  subject  will  be  found  in  the  chapter 
on  the  blood  in  infancy. 


The  Leucocytosis  of  Pregnancy. 

Most  primiparce  show  during  the  latter  montJis  of  pregnancy  a 
moderate  increase  of  all  varieties  of  leucocytes.  Thirteen  thou- 
sand cells  per  cubic  centimetre  is  about  the  average  count. 

In  multipart  it  occurs  in  only  about  fifty  per  cent  of  the 
cases.  Digestion  leucocytosis  "on  top  of"  the  constant  preg- 
nancy leucocytosis,  so  to  speak,  does  not  occur. 

As  mentioned  above,  the  relative  percentage  of  the  different 
types  of  leucocyte  remains  unchanged,  so  that  all  varieties  must 
be  equally  increased  (eosinophiles  excepted).  The  fact  that 
digestion  does  not  increase  the  pregnancy  leucocytosis,  leads 
to  the  suggestion  that  the  whole  thing  may  be  only  a  prolonged 
digestion  leucocytosis— the  mother  having  to  eat  for  two.  The 
swelling  of  thejbreasts  may  also  account  for  part  of  the  leuco- 


102  CLINICAL   BLOOD    EXAMINATION. 

cytosis.  In  the  last  weeks  of  pregnancy  the  leucocytosis 
increases  till  at  the  beginning  of  labor  it  is  often  16,000  to 
18,000.  It  has  no  diagnostic  value,  as  it  is  not  present  during 
the  earlier  months  of  pregnancy  when  diagnosis  is  difficult,  and 
in  the  later  months  such  conditions  as  hydatiform  mole  and 
fibroid  tumors  might  raise  the  count  of  white  cells  as  much  as 
pregnancy. 

Leucocytosis  After  Parturition. 

The  following  charts  illustrate  the  course  of  the  leucocyte 
curve  from  the  time  of  parturition  till  the  end  of  the  second  week 
after  it. 

All  were  primiparae  excepting  Nos.  5,  8,  and  9.  There  was 
no  sepsis  in  any  case,  and  the  temperature  charts  were  practi- 
cally normal  after  the  second  day.  No  reasons  are  known  for 
the  variations  between  the  different  cases.  All  were  counted  at 
the  same  hour  of  the  day,  and  under  the  same  conditions  of 
nutrition.  All  nursed  their  children. 

The  only  importance  of  this  leucocytosis  is  that  it  might  be 
confounded  with  a  pathological  leucocytosis  in  a  case  suspected 
of  being  septic.  Just  how  long  the  leucocytosis  is  prolonged 
during  lactation  has  not  been  studied  so  far  as  I  am  aware,  but 
it  certainly  may  go  on  several  weeks. 

Violent  exercise,  massage,  and  short  cold  baths  have  been 
shown  to  cause  a  temporary  increase  in  the  number  of  leuco- 
cytes in  the  peripheral  blood,  all  varieties  of  the  cell  being  equally 
increased.  The  explanation  usually  given  is  that  the  blood 
is  concentrated  by  vasomotor  contraction  and  rise  of  blood 
pressure. 

Schultz  (Deut.  Arch.  f.  Idin.  Med.,  1893,  page  234)  found  the 
leucocytosis  of  exercise  amount  to  about  the  same  as  that  of 
digestion,  11,000  to  13,000.  He  also  noted  that  in  dogs 
merely  opening  the  peritoneum  aseptically  or  breaking  a  leg 
caused  leucocytosis. 

Thayer  studied  twenty  cases  of  typhoid  and  found  an  aver- 
age of  7,724  white  cells  before  and  13,170  after  a  Brand  bath 
(Johns  Hopkins  Medical  Bidletin,  April,  1893).  The  increase 
took  place  equally  in  all  varieties.  Winternitz  (Imperio-Koyal 
Medical  Society,  Vienna,  February,  1893)  came  to  a  similar 
conclusion  and  found  also  that  prolonged  cold  bathing  decreased 


LEUCOCYTOSI8. 


103 


the  number  of  white  cells  (dry  cold  does  the  same) .  A  patient 
was  recently  brought  to  the  Massachusetts  Hospital  who  had 
fallen  through  a  hole  in  the  ice  and  been  some  minutes  in  the 


s       a 


II 

'—    ^ 

s-  a 
1-1 

g      w   g 

I! 

5  ^ 

c8    O 

.2  2 


icy  water.  His  temperature  was  91.8°  by  the  rectum.  Blood 
count  showed  17,500  leucocytes  per  cubic  millimetre.  Next 
day  he  was  perfectly  well.  On  the  contrary,  short  hot  baths 
decrease  and  prolonged  ones  increase  the  number  of  leucocytes. 


104 


CLINICAL   BLOOD    EXAMINATION. 


Local  arm  baths  have  a  similar  effect,  raising  the  count  of 
leucocytes  in  the  blood  of  the  immersed  arm  if  cold  and  short, 
and  lowering  it  if  hot  and  short,  while  prolonged  immersion 
has  an  opposite  effect.  In  the  other  arm  the  counts  go  up  when 


M 

aj 

— 

ffl 

7T 

\ 

- 

• 

J* 

11 

s 


B    ^i 

K       00    O 

•    £§> 
V    A 

V     05 

,£3    0> 


il 


•3 


I 


1 

a 


1    8       8 


•those  of  the  immersed  arm  go  down,  and  vice  versa  (Eovighi).1 
JMitchell 2  found  that  the  leucocytes  showed  distinct  increase  (as 

!Arch.  Ital.  d.  Clin.  Med.,  xxxii.,  3,  1893. 

2  American  Journal  of  the  Medical  Sciences,  May,  1894. 


LEUCOCYTOSIS.  105 

well   as  the  red  cells  and  haemoglobin)  after   one  hour's  gen- 
eral massage. 

All  these  forms  of  leucocytosis  are  usually  explained  b^ 
changes  in  blood  pressure,  and  vasomotor  changes  affecting  the 
calibre  of  the  peripheral  vessels  and  consequently  their  con- 
tents. 

Terminal  Leucocytosis. 

The  leucocytosis  of  the  moribund  state,  though  by  no  means 
invariable,  occurs  in  many  cases,  whether  from  the  influence  of 
a  terminal  infection  or  from  stasis.  Where  death  is  sudden  or 
rapid  it  does  not  occur.  It  seems  to  be  analogous  to  the  ter- 
minal rise  of  temperature  seen  at  the  close  of  many  chronic 
non-febrile  affections.  The  longer  the  patient  is  moribund  the 
higher  the  count  reaches.  In  pernicious  anaemia  the  increase 
may  be  so  great  as  to  simulate  lymphatic  leukaemia.  Such  a 
case  occurred  in  the  writer's  own  experience.  The  patient  had 
presented  the  signs  and  symptoms  of  pernicious  anaemia,  and 
the  blood  was  typical  of  the  disease  in  all  respects  except  for 
the  lack  of  nucleated  red  cells. 

Slides  taken  on  the  day  of  death  showed  a  ratio  of  one  white 
to  fifteen  red  cells,  the  small  lymphocytes  greatly  predominat- 
ing, but  the  autopsy  revealed  simply  the  lesions  of  pernicious 
anaemia.  The  differential  count  of  one  thousand  leucocytes  on 
the  day  of  death  showed:  Lymphocytes,  91.7  per  cent;  poly- 
morphonuclear  cells,  7.7  per  cent;  eosinophiles,  0.5  per  cent. 
Four  megaloblasts  were  seen  while  counting  these.  The  total 
leucocyte  count  was  unfortunately  not  made. 

In  ordinary  cases  the  differential  count  shows  an  increase  in 
the  polymorphonuclear  leucocytes.  Thus  in  a  case  reported  by 
Eieder,  in  which  the  leucocyte  count  rose  during  the  last  two 
days  of  life  from  7,800  to  59,300,  the  polymorphonuclear  cells 
constituted  87.5  per  cent  of  the  whole  59,300. 

PATHOLOGICAL  LEUCOCYTOSES. 

For  convenience'  sake  these  may  be  divided  as  follows : 

1.  Post-hem orrhagic  leucocytosis. 

2.  Inflammatory  leucocytosis. 

3.  Toxic  leucocytosis. 


106  CLINICAL   BLOOD   EXAMINATION. 

4.  Leucocytosis  in  malignant  disease. 

5.  Leucocyjosis    due   to   therapeutic   and  experimental  in- 
fluences. 

1.  Post-hemorrhagic  Leucocytosis. 

Within  an  hour  after  a  large  hemorrhage  we  find  commonly  a 
considerable  increase  (16,000-18,000).  In  hemorrhage  from  the 
stomach  this  disappears  again  usually  within  a  day  or  two, 
while  in  ordinary  traumatic  hemorrhage  it  persists  longer. 
This  last  fact  may  perhaps  be  explained,  as  v.  Limbeck  sug- 
gests, by  the  local  conditions  in  the  wound  rather  than  by  the 
loss  of  blood  in  itself. 

The  polymorphonuclear  leucocytes  are  usually  increased 
relatively  and  absolutely  as  in  other  forms  of  pathological  leu- 
cocytosis.  Sometimes  we  have  lymphocytosis  (see  page  114). 
The  degree  of  increase  in  the  white  cells  is  parallel  in  a  general 
way  to  the  anaemia  produced  in  the  individual,  i.e.,  it  depends 
on  his  powers  of  recuperation  rather  than  on  the  amount  of 
blood  lost.  Its  duration  follows  the  same  rule/ 

2.  Inflammatory  Leucocytosis. 

I  use  the  term  "inflammatory  leucocytosis"  rather  than 
"  leucocytosis  of  infectious  diseases"  because  there  is  a  consider- 
able number  of  infectious  diseases  in  which  no  leucocytosis  oc- 
curs, while  it  accompanies  almost  all  forms  and  cases  of  inflam- 
mation. Nevertheless  I  shall  class  under  this  heading  some 
diseases  in  which  inflammation  plays  but  a  very  subordinate 
role. 

I.  Although  purulent  and  gangrenous  processes  usually  cause 
a  higher  count  of  white  cells  than  serous  processes,  the  amount 
of  the  exudation  is  not  a  measure  of  the  amount  of  leucocytosis. 
It  seems  to  depend  rather  on  the  resultant  of  two  forces,  viz., 
the  severity  of  the  infection  and  the  resisting  power  of  the  indi- 
vidual.. These  factors  may  interact  in  various  ways : 

1.  Infection  mild  :          resistance  good         =  small  leucocytosis. 

2.  "         less  mild :         "          less  good  =  moderate  leucocytoeis. 

3.  "        severe:  "          good         =  very  marked  leucocytosis. 

4.  "  "  "          poor          ==  no  leucocytosis. 

1  Further  account  of  the  blood  after  hemorrhage  will  be  found  on  page 
126  et  seq. 


PATHOLOGICAL  LEUCOCYTOSIS.  107 

This  will  be  illustrated  later  under  "Pneumonia  "  and  under 
"Sepsis."  Experiments  on  animals  show  that  whereas  moder- 
ate sized  doses  of  septic  cultures,  not  sufficient  to  kill  the 
animal,  are  followed  by  leucocytosis,  larger  doses  after  which 
death  follows  speedily,  do  not  raise  the  leucocyte  count  at  all. 
Animals  weakened  by  any  cause  show  less  leucocytosis  to  a 
moderate  dose  than  strong  animals. 

If  the  individual  reacts  from  the  shock  his  leucocytes  are  in- 
creased again  and  rise  above  normal.  If  reaction  fails  the  leu- 
cocytes do  not  rise. 

II.  Inflammatory  leucocytoses  differ  from  physiological  leu- 
cocytoses — 

(a)  In  being  usually  of  larger  extent. 

(6)  In  being  almost  aways  accompanied  by  a  relative  and  ab- 
solute increase  in  the  percentage  of  polymorphonuclear  cells. 

III.  The  course  of  the  leucocytosis  as  regards  both  amount 
and  duration  shows,  like  the  temperature  chart,  certain  more  or 
less  characteristic  differences  in  different  diseases. 

IV.  In  some  cases  in  which  the  absolute  number  of  leuco- 
cytes is  not  increased,  we  see  a  relative  increase  in  the  polymor- 
phonuclear cells,  pointing  to  the  fact  that  influences  are  at  work 
similar  to  those  which  produce  an  absolute  increase. 

Y.  That  the  amount  of  exudation  is  not  of  itself  a  measure  of 
the  amount  of  leucocytosis  is  shown  by  the  fact  that  erysipelas 
or  scarlet  fever  may  be  accompanied  by  as  high  a  count  as  the 
average  count  in  pneumonia  or  empyema. 

That  purulent  exudations  usually  have  more  effect  on  the 
white  cells  than  do  serous  ones  is  due,  I  suppose,  to  the  fact 
that  a  purulent  inflammation  usually  means  a  severer  infection. 

YI.  No  direct  connection  exists  between  leucocytosis  and 
fever,  many  febrile  affections  running  their  course  with  a  normal 
leucocyte  count.  When  both  leucocytosis  and  fever  are  due  to 
the  same  causes  they  rise  and  fall  together,  but  the  correspond- 
ence is  rarely  accurate,  and  marked  leucocytosis  may  exist  with- 
out fever. 

VII.  Acute,  rapidly  spreading  inflammations  seem  to  pro- 
duce a  greater  leucocytosis  (other  things  being  equal)  than 
those  in  which  the  process  is  relatively  chronic  and  stationary. 
For  instance,  an  appendicitis,  when  well  walled  off  and  station- 
ary, shows  less  increase  in  white  blood  cells  than  while  its  le- 


108  CLINICAL   BLOOD   EXAMINATION. 

sions  are  progressing.  But  peracute,  overwhelming  general  sep- 
sis may  have  no  effect  on  the  leucocytes,  the  reactive  power  of 
the  organism  being  crushed. 

YIII.  Most  inflammatory  leucocytoses  are  preceded  by  a 
temporary  diminution  in  the  number  of  leucocytes.  This  oc- 
curs in  animals  from  shock  of  any  kind  (blows  on  the  head, 
tying  to  the  etherizing  board) ,  and  it  seems  not  unlikely  that 
the  cause  is  the  same  in  all  cases. 

The  following  is  a  list  of  the  more  important  inflammatory 
or  infectious  conditions  in  which  leucocytosis  appears: 

1.  Infectious  diseases  ivith  comparatively  slight  local  inflamma- 
tory processes : 

(a)  Asiatic  cholera. 

(b)  Relapsing  fever. 

(c)  Typhus  fever  (according  to  the  majority  of  observers). 

(d)  Scarlet  fever. 

(e)  Diphtheria  and  follicular  tonsillitis. 
(/)  Syphilis  (secondary  stage). 

(a)  Erysipelas. 
(h)  The  bubonic  plague. 
(i)  Yellow  fever  (some  cases) . 

2.  Infectious  diseases  with  more  extensive,  local  lesions : 
(a)  Pneumonia. 
(6)  Small-pox  (suppurative  stage). 

(c)  Malignant  endocarditis,    puerperal  septicaemia,    and  all 
pyaemic  and  septicsemic  conditions. 

(d)  Actinomycosis. 

(e)  Trichinosis. 
(/)  Glanders. 

(g)  Acute  multiple  neuritis  (febrile  stages). 
(h)  Acute  articular  rheumatism. 
(i)  Septic  meningitis  and  cerebro-spinal  meningitis. 
(J)  Cholangitis,  cholecystitis,  and  ernpyema  of  the  gall  blad- 
•der. 

(k)  Acute  pancreatitis. 

(I)  Endometritis,  cystitis  (some  acute  cases). 

(m)  Gonorrho3a. 

3.  Local  inflammatory  processes : 

(a)  Abscesses  of  all  kinds  and  situations,  such  as 

Felon. 


PATHOLOGICAL  LEUCOCYTOSIS.  109' 

Carbuncle,  furunculosis. 

Tonsillar  and  retropharyngeal  abscess. 

Appendicitis,  phlebitis  (some  cases). 

Pyonephrosis,  perinephritic  abscess  and  pyelonephritis. 

Osteomyelitis,  empyema. 

Psoas  and  hip  abscess  when  not  simply  tubercular. 

Abscess  of  lung,  liver,  spleen,  ovary,  prostate. 

Salpingitis  and  pelvic  peritonitis,  epididymitis. 

(b)  Inflammations  of  the  serous  membranes  including : 
Pericarditis,  peritonitis,  arthritis  (serous  or  purulent,  non- 
tubercular),  conjunctivitis. 

(c)  Gangrenous  inflammations,  as  of  the 
Appendix,  lung,  bowel,  mouth  (noma). 

(d)  Many  inflammatory  skin  diseases,   such  as  dermatitis, 
pemphigus,  pellagra,  herpes  zoster,  prurigo,  some  cases  of  uni- 
versal eczema,  etc. 

3.   Toxic  Leucocytosis. 

Under  this  heading  I  have  grouped  most  of  the  conditions 
not  obviously  to  be  explained  as  infectious  or  inflammatory 
(though  some  may  turn  out  to  be  such)  and  not  due  to  malig- 
nant disease  or  therapeutic  agencies.  This  classification  is 
chiefly  for  convenience'  sake  and  represents  only  a  guess  at  the 
real  explanation  of  the  leucocy tosis : 

(a)  Leucocytosis  of  illuminating-gas  poisoning. 

(b)  "  quinine  poisoning. 

(c)  "  rickets  (many  cases). 

(d)  "  the  uric-acid  diathesis,  gout. 

(e)  "  acute  yellow  atrophy  of  the  liver.    . 

(/)  "  advanced    cirrhosis   of  the    liver   (some 

cases)  especially  with  jaundice. 
(g)  "  acute    gastro-intestinal    disorders    (pto- 

mains  ?) . 
(li)  "  chronic     nephritis,    usually    in    ursemic 

cases. 
(i)  after  injections  of  tuberculin  and  thyroid 

extract. 

(/)  after  injection  of  normal  salt  solution  (in- 

travenous) . 

(k)  after  ingestion  of  salicylates. 

(?)  during  and  after  etherization. 


HO  CLINICAL   BLOOD   EXAMINATION. 

Possibly  the  leucocytosis  of  acute  delirium  belongs  also  in 
this  group. 

4.  Leucocytosis  of  Malignant  Disease. 

Very  likely  this  belongs  more  properly  under  one  or  another 
of  the  classes  just  mentioned.  Some  observers  think  that  it  oc- 
curs only  from  the  inflammation  excited  in  the  periphery  of 
some  malignant  tumors ;  others  that  it  is  due  to  absorption  of 
morbid  products  from  the  tumor  itself ;  others  again  that  it  is 
to  be  accounted  for  by  the  cachectic  state  associated  with  the 
growth  of  the  tumors.  The  details  and  conditions  of  its  occur- 
rence will  be  discussed  later  (page  332). 

5.  Leucocytosis  Due  to  Therapeutic  and  Experimental  Influences. 

Pohl '  found  that  most  of  the  so-called  tonics  and  stomachics 
produce  a  slight  increase  in  the  white  cells  in  animals,  particu- 
larly the  vegetable  tonics  like  tincture  of  gentian,  and  oil  of 
anise  seed,  while  bismuth,  bicarbonate  of  soda,  and  iron  had  no 
such  effect.  Quinine,  caffeine,  and  ethyl  alcohol  gave  likewise 
negative  results.  Yon  Limbeck  found  leucocytosis  in  men  after 
oil  of  peppermint  and  oil  of  anise  seed. 

Binz 2  got  the  same  results  with  camphor.  In  all  these  ex- 
periments the  substances  were  given  by  the  mouth. 

Using  subcutaneous  or  intravenous  injections,  Lowit  experi- 
mented on  animals  with  hemialbumose,  peptone,  pepsin,  nucle- 
inic  acid,  nuclein,  extract  of  blood-leech,  pyocyanin,  tuberculin, 
curare,  uric  acid,  urate  of  sodium,  and  urea.  All  but  the  last 
of  these  produce  temporary  decrease  followed  by  increase  of 
leucocytes. 

Goldschneider  and  Jacob 3  used  extracts  of  various  organs. 
Extract  of  spleen,  marrow,  and  thymus  produced  leucocytosis 
preceded,  as  in  Lowit' s  experiments,  by  a  brief  diminution  in 
the  number  of  leucocytes,  while  extract  of  pancreas,  thyroid, 
kidney,  and  liver  had  no  effect. 

Winternitz  4  injected  a  large  variety  of  substances  subcutane- 

'Arch.  f.  exp.  Path.  u.  Pharm.,  1889,  vol.  xv. 
8  Arch.  f.  exp.  Path.  u.  Pharm.,  vol.  v.,  p.  122. 
3  Arch.  f.  Anat.  u.  Physiol.,  1893,  p.  567. 
4 Arch.  f.  exp.  Path.  u.  Pharm.,  vol.  xxxv.,  p.  77. 


PATHOLOGICAL   LEUCOCYTOSIS.  Ill 

ously  and  found  that  the  degree  of  leucocy tosis  was  parallel  to 
the  degree  of  local  reaction  excited. 

For  example,  neutral  salts  and  weak  acids  or  alkalies  pro- 
duced slight  local  inflammation  and  a  leucocy  tosis  of  from  forty 
to  seventy -five  per  cent  of  the  original  count.  But  irritants  like 
turpentine,  croton  oil,  nitrate  of  silver,  sulphate  of  copper, 
mercury,  antimony,  digitoxin,  etc.,  produced  local  suppuration 
(aseptic)  and  much  greater  leucocytosis  (two  hundred  to  three 
hundred  per  cent). 

Pilocarpine  and  antipyrin  have  been  found  by  v.  Jaksch  and 
others  to  produce  marked  increase  in  the  number  of  leucocytes 
when  given  subcutaneously .  During  the  use  of  thyroid  ex- 
tract Kichter  (Centralblatt  f.  inn.  Med.,  1896,  p.  3)  noted 
leucocytosis. 

A  large  number  of  observations  on  the  effects  of  injections 
of  bacteria  or  their  toxins  agree  in  the  following  results. 

1.  Where  the  dose  is  very  large  the  leucocytes  are  reduced, 
and  the  animal  dies. 

2.  Where  the  dose  is  not  sufficient  to  kill  the  animal  the 
temporary  diminution  in  the  leucocytes  is  soon  followed  by  leu- 
cocytosis. 

3.  Where  the  dose  is  slowly  fatal  the  count  of  leucocytes 
oscillates  up  and  down  within  wide  limits. 

4.  Animals  previously  rendered  immune  to  the  poison  in- 
jected show  little  or  no  leucocytosis. 

5.  Leucocytosis  is  more  easily  called  forth  and  of  greater  ex- 
tent in  young  animals. 

6.  Most  pathogenic  organisms  act  similarly,  but  bacilli  and 
toxins  of  tuberculosis  as  a  rule  cause  no  leucocytosis. 

7.  There  is  no  evidence  that  any  one  variety  of  leucocyte  is 
attracted  by  any  particular  bacillus  or  toxin. 

In  the  above  sketch  of  therapeutic  and  experimental  forms  of 
leucocytosis  no  attempt  has  been  made  to  give  anything  but 
the  more  interesting  and  important  outlines  of  the  immense 
amount  of  work  done. 

Cell  Structure  of  the  Leucocytes  in  Leucocytosis. 

Hitherto  we  have  spoken  as  if  leucocytosis  meant  only  an 
increased  number  of  the  normal  cells,  but  one  cannot  study  the 
cell  forms  in  extensive  pathological  leucocytosis  without  noting 


112 


CLINICAL   BLOOD   EXAMINATION. 


in  many  cases  qualitative  changes  in  the  individual  cells.     These 
are  chiefly : 

1.  A  greater  or  less  approximation  of  the  nuclei  of  polymor- 
phonuclear  neutrophiles  to  the  appearances  of  the  myelocyte 
nucleus.  As  will  be  mentioned  later  under  leukaemia,  we  find  in 
every  blood  containing  many  myelocytes  numerous  cells  whose 
nucleus  is  on  the  border-line  between  the  myelocyte  and  the 
polymorphonuclear  stage,  so  far  as  appearances  go.  Now  in 
leucocytosis  we  find  the  same  "border-line"  cells  in  smaller 


FIG.  29.— Atypical  Leucocytes  seen  in  Leucocytosis.  1,  Leucocytes  with  polar  arrange- 
ment of  nuclei  (mitosis?);  2  and  3,  leucocytes  with  nuclei  resembling  those  of  myelo- 
cytes; 4,  leucocyte  containing  two  kinds  of  granules. 

numbers,  the  likeness  to  the  myelocyte  sometimes  passing  into 
identity  in  one  to  three  per  cent  of  the  cells. 

2.  A  greater  or  less  approximation  of  the  appearance  of  the 
large  lymphocytes'  protoplasm  to  that  of  myelocyte  protoplasm, 
i.e.,  a  diffuse  violet  or  purple  color  exactly  as  in  the  myelocyte 
but  non-granular.     Engel  makes  a  separate  variety  of  this  cell, 
giving  it  the  useless  name  of  "  mononuclear  cell. " 

3.  Other  finer  changes,  such  as  the  number,  size,  and  stain- 
ing power  of  the  neutrophilic  granulations,  polar  position  of  the 
nuclei,  etc.  (see  Fig.  29),  require  further  study. 


PATHOLOGICAL   LEUCOCYTOSIS.  113 

Changes  like  the  above  militate  against  the  idea  that  leu- 
cocytosis is  simply  a  matter  of  distribution  in  the  peripheral  or 
internal  vessels. 

Absence  of  Leucocytosis. 

It  is  of  fully  as  great  a  practical  assistance  to  us  to  know 
that  in  certain  infective  diseases  leucocytosis  is  regularly  absent 
as  to  know  those  conditions  in  which  it  is  to  be  expected. 
Among  the  most  important  diseases  in  which  leucocytosis  is 
conspicuously  absent  are : 

(a)  Typhoid  fever. 

(6)  Malaria. 

(c)  Grippe  (most  cases). 

(d)  Measles. 

(e )  Rotheln  and  mumps. 
(/)  Cystitis. 

(  g)  Tuberculosis,  including — 
Incipient  phthisis. 
Miliary  tuberculosis. 
Tubercular    peritonitis. 

ostitis  and  periostitis, 
pleurisy, 
pericarditis. 1 

In  some  of  these  affections,  notably  in  miliary  tubercle  and 
the  later  weeks  of  typhoid,  the  leucocytes  are  diminished. 
Further  details  will  be  given  under  the  special  diseases. 

LEUCOPENIA. 

Definition. — A  diminution  in  the  number  of  white  cells  in 
the  peripheral  circulation  as  compared  with  the  number  normal 
for  the  given  individual. 

1.  The  effects  of  starvation  and  malnutrition  in  producing 
leucopenia  have  already  been  described.     Such  leucopenia  is 
usually  associated  with  lymphocytosis  (see  below).     Cancer  of 
the  gullet  is  an  example  of  this  class. 

2.  Short  hot  baths  or  prolonged  cold  baths  produce  tem- 
porarily the  same  result  (Winternitz,  loc.  cit.). 

1  Tubercular  meningitis  often  does  show  leucocytosis  (vide  infra,  page 

266). 


114  CLINICAL   BLOOD   EXAMINATION. 

3.  Most  of  the  infective  diseases  in  which  there  is  no  leuco- 
cytosis  are  sometimes  characterized  by  leucopenia,  e.g.,  grippe, 
measles,   miliary  tuberculosis,  and  other  forms  of  pure  tuber- 
cular infection,   malaria,   and  especially  typhoid,  in  the  later 
weeks  of  which  it  is  almost  invariable,  and  is  accompanied  by 
lymphocytosis. 

Where  a  case  of  leukaemia  is  complicated  by  an  infective 
disease  (pneumonia,  septicaemia)  the  number  of  leucocytes  may 
fall  below  the  normal.  In  a  case  recently  occurring  at  the  Mass- 
achusetts General  Hospital  in  which  a  lymphatic  leukaemia 
was  terminated  by  septicaemia  from  glandular  suppuration,  the 
white  cells  fell  gradually  from  40,000  three  weeks  before  death 
to  419  per  cubic  millimetre  on  the  day  of  death.  I  have  never 
heard  of  a  lower  count  than  this.  The  differential  count  was 
unchanged  (lymphocytes  —  ninety-eight  per  cent). 

4.  In  pernicious  anaemia  the  count  is  usually  very  low  and 
may  fall  below  1,000  cells  per  cubic  millimetre.     Other  forms  of 
anaemia  (rachitic,  syphilitic)  occasionally  produce  the  same  re- 
sult. 

LYMPHOCYTOSIS. 

Lymphocytosis  is  a  relative  increase  in  the  lymphocytes  in  the 
blood,  with  or  tvithout  an  increase  of  the  total  leucocytes  count 
The  increase  is  relative  to  the  percentage  of  lymphocytes  normal 
for  the  individual.  When  lymphocytosis  and  an  increase  of  the 
total  leucocyte  count  are  present  we  cannot  distinguish  the 
blood  from  that  of  lymphatic  leukaemia,  and  the  distinction 
must  depend  upon  the  course  and  symptoms  of  the  case. ' 

1.  Such  a  condition  (relative  to  the  adult)  occurs  in  healthy 
infant's  blood  and  in  many  diseases  of  infancy,  the  blood  seem- 
ing to  have  a  tendency  to  return  to  the  infantile  type.  This  is 
especially  true  of  cholera  infantum  and  any  gastro-intestinal 
trouble.  Anything  that  retards  the  infant's  normal  gain  in 
weight  or  general  development  retards  its  blood  development  as 
well.  Thus  a  child  of  three,  convalescent  from  a  summer  diar- 
rhoea, may  have  fifty  to  sixty  per  cent  of  lymphocytes,  which 

1  The  lymphocytosis  of  chlorosis  has  been  mistaken  for  lymphatic 
leukaemia  (Schreiber)  owing  to  too  exclusive  reliance  on  the  results  of  the 
blood  examination.  The  patient  recovered.  Such  cases  are  very  rare,  and 
the  difficulty  hardly  ever  arises. 


LYMPHOCYTOSIS.  115 

would  be  normal  for  an  infant  of  a  few  weeks,  but  for  three 
years  old  is  very  high. 

2.  Hereditary  syphilis  is  perhaps   the  best-known  cause  of 
relative  lymphocytosis  in  children.     Scurvy  may  produce  the 
same  result.     Dividing  the  anaemias  of  children  into  two  groups, 
those  that  do  and  those  that  do  not  produce  leucocytosis,  it 
appears  that  the  great  majority  of  those  whose  total  leucocyte 
count  is  normal  show  a  relative  lymphocytosis.     This  is  the  case 
irrespective  of  whether  there  is  enlargement  of  the  spleen  or  not. 

Sometimes  the  smaller,  sometimes  the  larger  lymphocytes 
are  in  the  majority.  Often  no  division  between  the  two  kinds  is 
possible. 

3.  In  adults  some  forms  of  debility  may  be  associated  with 
relative  lymphocytosis  as  above  noted   (page  97).     It  is  most 
marked,  however,  in  chlorosis,  pernicious  anaemia,  and  the  anae- 
mia secondary  to  syphilis,  in  the  later  weeks  of  typhoid  fever 
and  in  lactation. 

4.  Certain  cases  of  Graves'  disease  show  marked  lymphocy- 
tosis.    How  such  cases  differ  from  those  that  do  not  show  it  I 
have  not  been  able  to  determine. 

5.  It   occurs  also  in  haemophilia,    goitre,  in  some   cases  of 
cervical  adenitis,  whether  tubercular  or  lymphomatous,  and  in 
tumors  of  the  spleen. 

6.  During  the  administration  of  thyroid  extract  a  lymphocy- 
tosis has  been  recently  noted  by  Perry  (New  York  Medical  Rec- 
Becord,  August  29th,  1896). 

7.  The  larger  forms  of  lymphocytes  are  increased  in  some 
splenic  tumors  (chronic  "  ague  cake"),  at  the  end  of  scarlet  fever, 
iu  imeumonia  with  delayed  resolution  (some  cases),  in  measles, 
certain  forms  of  phthisis  and  in  the  non-suppurative  stages  of 
small-pox ;  also  in  many  of  the  same  diseases  in  which  the  small 
lymphocytes  are  increased. 

8.  So  far  I  have  referred  chiefly  to  relative  lymphocytosis. 
Absolute  lymphocytosis  is  very  rare  outside  of  lymphatic  leu- 
kaemia.    One  case  occurred  at  the  Massachusetts  General  Hos- 
pital in  1894 — a  child  of  six,  who  passed  through  an  attack  of 
bronchopneuinonia  with  uneventful  recovery,  the  only  pecu- 
liarity of  the  case  being  the  marked  increase  of  white  cells  run- 
ning up  to  94,600,  sixty-nine  per  cent  of  which  were  lymphocytes. 
During  convalescence  the  blood  became  normal  and  the  child 


116  CLINICAL  BLOOD   EXAMINATION. 

left  the  hospital  well  in  all  respects.     The  case  will  be  referred 
to  later  in  the  account  of  the  blood  of  pneumonia. 

Diagnostic  Value  of  Lymphocytosis. 

1.  I  have  already  suggested  that  the  degree  of  health  in 
persons  not  organically  diseased  might  perhaps  prove  to  vary 
directly  with  the  percentage  of  polymorphonuclear  cells  in  the 
blood. 

2.  In  children  the  same  percentage  is  to  a  certain  extent  a 
measure  of  the  child's  degree  of  development — causes  of  leu- 
cocytosis  being  excluded,  and  the  percentage  normal  for  a  child 
of  the  patient's  age  being  taken  as  the  standard. 

3.  The    diagnosis   of    obscure   syphilitic    disease    may   be 
supported  by  the  coincidence  of  lymphocytosis    with   eosino- 
philia. 

4.  Absolute   lymphocytosis   in   the   presence   of    glandular 
tumors  is  our  mainstay  in  the  diagnosis  of  lymphatic  leukaemia. 

EOSINOPHILIA. 

Definition. — An  increase  in  the  percentage  of  eosinophiles  in 
the  circulatory  blood,  with  or  without  an  increase  in  the  total 
leucocyte  count. 

The  researches  of  Neusser,  Zappert,  Weiss,  Klein,  and  others 
have  brought  the  eosinophilic  cells  once  more  into  the  promi- 
nence which  they  lost  when  it  became  apparent  that  they  were 
in  no  way  peculiar  to  leukaemia. 

1.  Leukaemia  is   occasionally  associated  with  eosinophilia 
(see  below,  page  167),  but  in  the  majority  of  cases  this  is  not  so. 
As  in  normal  blood,  from  one  to  three  per  cent  of  them  are  to 
be  found. 

2.  In  infancy  the  percentage  of  eosinophiles  is  very  often 
higher  than  in  adults,  so  that  in  them  eosinophilia  may  be  con- 
sidered physiological.     In  adults  its  presence  is  often  unex- 
plained.    The  eosinophiles  are  the  most  seemingly  capricious 
of  all  blood  cells.     A  certain  amount  of  light  has  been  thrown 
on  them  by  the  observations  of  Neusser  and  his  pupils  (Weiss, 
Schreiber,  Klein,  ai)d  others). 

3.  Neusser  noticed  that  eosinophilia  occurs — 


EOSINOPHILIA.  117 

(A)  In  many  affections  of  the  bones  (sarcoma,  leukaemia, 
osteomalacia). 

(B)  In  many  affections  of  the  skin  (pemphigus,  pellagra,  and 
others). 

(C)  In  troubles  involving  the  female  genitals,  especially  the 
ovaries. 

(D)  In  disturbances  of  the  sympathetic  nervous  system. 

That  there  is  some  relation  between  these  seemingly  uncon- 
nected sets  of  phenomena  is  shown  by  various  other  facts  besides 
the  presence  of  eosinophilia  in  them  all. 

(a)   Bone  and  genitals. 

Osteomalacia  is  most  apt  to  occur  in  pregnancy  and  is  cured 
in  some  cases  by  castration. 

(6)  Genitals  and  sympathetic  nervous  system. 

The  presence  of  all  sorts  of  psychoses  and  vasomotor  troubles 
associated  with  menstruation,  pregnancy,  and  the  climacteric, 
and  the  so-called  "  reflex"  disturbances  in  connection  with  uter- 
ine or  ovarian  disease,  are  well  known. 

(c)  The  connection  of  the  skin  with  both  of  the  last-men- 
tioned systems  is  seen  in  the  trophic  disorders  and  sympathetic 
dermatoses  of  hysteria  and  ovarian  disease. 

Working  out  the  suggestions  of  this  theory  Neusser  and  his 
pupils  have  found  relative  eosinophilia  in  the  following  affec- 
tions : 

1.  Bones. 

Osteomalacia,  malignant  bone-tumors,  pernicious  anaemia 
(some  cases),  splenic-nay elogenous  leukaemia  (occasionally). 
[The  writer  has  seen  slight  eosinophilia  in  osteomyelitis.] 
Possibly  the  relative  eosinophilia  of  normal  infants'  blood  may 
be  connected  with  the  great  activity  of  their  bone  growth. 

2.  Diseases  affecting  the  skin. 

Urticaria,  pellagra,  dermatitis  herpetiformis,  and  pemphi- 
gus (constantly) ;  some  varieties  of  herpes,  prurigo,  eczema, 
lymph odermia  perniciosa ;  after  vaccination,  in  scarlet  fever  and 
syphilis  (not  measles  or  small-pox),  ichthyosis,  lupus,  myx- 
oedema.1 

1 1  do  not  vouch  for  these  or  for  any  of  Neusser's  statements,  which  are 
frequently  incorrect.  In  a  single  case  each  of  pemphigus  and  prurigo  I 
have  found  only  four  per  cent  and  three  per  cent  of  eosinophiles.  On  the 


118  CLINICAL  BLOOD  EXAMINATION. 

3.  Genitals. 

Gonorrhoea,  prostatitis,  many  ovarian  tumors,  before  and 
during  the  early  days  of  menstruation,  puerperal  mania,  and 
the  psychoses  'of  menstruation,  of  the  puerperium,  and  of  the 
climacteric;  in  sexual  neurasthenia,  after  coitus,  and  in  lacta- 
tion. 

4.  Sympathetic  Nervous  System. — The  psychoses  last  men- 
tioned, hysteria,  Basedow's  disease,  and  some  of  those  given 
under  the  next  heading. 

5.  Besides  these  general  groups,  Neusser  has  noticed  another 
class  of  cases  characterized  by  eosinophilia,  namely,  those  in 
which  some  member  of  the  group  of  xanihin  bases  is  supposed 
to  be  in  the  system.     In  the  so-called  uric-acid  diathesis  the 
nuclein  derivatives  are  transformed  in  the  intestine  into  one  of 
the  xanthin  bases,  and  their  presence  in  the  system  appears  to 
give  rise  to  eosinophilia. 

At  any  rate  we  regularly  find  eosinophilia  (according  to 
Neusser)  in  diseases  thought  to  be  characterized  by  an  excess  of 
these  substances  in  the  system.  Examples  of  this  are  found  in 
gout,  bronchial  asthma,  emphysema,  certain  forms  of  migraine 
and  epilepsy,  oxaluria,  uraemia,  tetanus,  some  gastro-intestinal 
troubles,  ankylostomiasis,  after  injections  of  nuclein,  pilocar- 
pine,  tuberculin,  iron  preparations,  and  in  most  non-malignant 
liver  diseases.  All  these  Neusser  believes  stimulate  the  sym- 
pathetic nervous  system  and  hence  the  bone  marrow,  through 
the  production  of  xanthin  bases.  In  asthmatic  patients  he  suc- 
ceeded in  producing  a  paroxysm  by  injecting  nuclein  subcuta- 
neously. 

Possibly  under  this  heading  comes  the  eosinophilia  after 
antipyrin,  and  that  sometimes  found  in  chlorosis,  scurvy, 
nephritis,  chronic  malaria,  and  phthisical  patients  with  cavities. 
In  the  latter  cases  it  has  been  suggested  that  the  patients  may 

other  hand,    in  a  case  of  dermatitis  herpetiformis  in  which  I  lately  ex- 
amined, the  differential  count  of  five  hundred  cells  showed  : 

Poymorphonuclear  neutrophiles,      .         .         .  47  per  cent. 

Small  lymphocytes,   .......  25        " 

Large  " 8        " 

Eosinophiles, 19        " 

Myelocytes,         .  1        " 


EOSINOPHILES.  119 

inoculate  themselves  with  tuberculin  absorbed  from  their  lung 
cavities. 

6.  Tumors  of  the  spleen  are  also  accompanied  by  eosinophilia 
in  some  cases.  Neusser  does  not  explain  this  under  the  theory 
above  sketched. 

Many  acute  mental  troubles  show  eosinophilia,  while  chronic 
cases  do  not. 

Other  causes  of  eosinophilia  are  phosphorus  poisoning  and 
injections  of  campherin. 

In  Osier's  clinic  there  have  recently  been  observed  three  cases 
of  trichinosis  in  which  the  eosinophilic  cells  were  from  the 
first  increased,  and  continued  to  increase  till  in  one  case  at  the 
time  of  death  there  was  68  per  cent  of  eosinophiles  in  a  leu- 
cocytosis  of  17,000.  I  have  had  one  similar  case. 

We  also  find  eosinophilia  in  some  cases  of  syphilis  and 
syphilitic  disease  of  the  spinal  cord  (tabes  dorsalis). 

DIMINUTION  IN  EOSINOPHILES. 

1.  During  digestion. 

2.  After  castration. 

3.  In  febrile  stages  of  pneumonia,  grippe,  typhoid,  diph- 
theria, sepsis,  and  most  infectious  diseases  accompanied  by  leu- 
cocytosis.     That  this  is  not  due  simply  to  the  presence  of  fever 
is  shown  by  the  fact  that  in  malaria  and  scarlet  fever,  despite 
high  fever,  eosinophiles  may  be  increased. 

4.  In  the  moribund  state  eosinophiles  are  diminished  or 
absent. 

In  the  post-critical  stages  of  pneumonia  and  other  infectious 
diseases  the  eosinophiles  swing  up  above  the  normal. 

4.  Malignant  disease,  hemorrhage,  and  most  of  other  causes, 
of  leucocytosis  also  diminish  the  eosinophiles. 

DIAGNOSTIC  AND  PROGNOSTIC  VALUE  OF  EOSINOPHILIA. 

Neusser  has  suggested  the  following  points : 1 

1.  In  the  diagnosis  between  puerperal  mania  and  puerperal 
sepsis,  eosinophilia  points  to  the  former. 

2.  Between  a  tumor  connected  with  the  genital  system  and 
one  not  so  connected,  eosinophilia  points  to  the  former. 

1  For  none  of  which  I  can  vouch. 


120  CLINICAL   BLOOD    EXAMINATION. 

3.  In  determining  whether  a  given  case  of  hysteria,  neurosis, 
or  psychosis  is  likely  to  be  benefited  by  castration,  the  presence 
of  eosinophilia  favors  the  operation. 

4.  In  malignant  disease  an  eosinophilia  points  to  a  metas- 
tasis in  the  osseous  system  (tumors  of  the  spleen  are  not  in- 
cluded in  this  rule) . 

5.  In  cases  of  doubtful  syphilis  eosinophilia  combined  with 
lymphocytosis  (see  above)  speaks  in  favor  of  syphilis. 

6.  The  diagnosis  of  any  obscure  form  of  "  uric-acid  diathesis" 
is  helped  by  finding  an  increase  of  eosinophiles. 

7.  In  distinguishing  malignant  liver  disease  from  other  liver 
disease  eosinophilia  points  to  the  latter. 

1.  In  the  prognosis  of  chlorosis,  eosinophilia  is  favorable. 

2.  In  the  prognosis  of  scarlet  fever  and  scarlatinal  nephritis 
the  greater  the  eosinophilia  the  better  the  prognosis. 

3.  After  hemorrhage  increased  eosinophiles  show  active  re- 
generation of  blood  and  good  prognosis. 

4.  In  pernicious  anaemia  eosinophilia  is  favorable  for  the 
same  reason. 

MYELOCYTES. 

The  occurrence  of  the  myelocyte  of  Ehrlich  in  the  circulat- 
ing blood  is  always  to  be  looked  upon  as  pathological,  that  is, 
as  the  intrusion  of  a  variety  of  leucocyte  naturally  a  stranger  to 
the  circulating  blood  and  a  permanent  inhabitant  of  the  marrow. 
Although  it  is  so  close  morphologically  to  other  varieties  of 
leucocytes  that  we  should  certainly  suppose  it  to  be  an  inter- 
mediate stage  between  the  large  lymphocytes  and  the  polymor- 
phonuclear  neutrophiles,  the  fact  that  it  does  not  occur  outside 
the  marrow  in  health  speaks  against  the  supposition. 

Of  the  occurrence  of  the  myelocyte  in  leukaemia  and  perni- 
cious anaemia  mention  will  be  made  under  those  diseases.  The 
object  of  this  section  is  to  give  a  list  of  the  other  conditions 
under  which  it  appears. 

Neusser '  has  found  small  percentages  of  myelocytes  in  urae- 
mia, carbonic-acid  poisoning,  diabetes,  syphilis,  puerperal 
mania,  osteomalacia,  Basedow's  disease,  and  sarcoma,  also  dur- 
ing menstruation. 

1  Cited  in  Klein:  Volkmann's  "Saraml.  klin.  Vortrage,"  December, 
1893. 


MYELOCYTES.  121 

Capps  found  considerable  percentages  near  death  in  general 
paralysis  (see  Book  II.,  page  313). 

J.  J.  Thomas  found  them  in  myxcedema. 

The  majority  of  other  references  to  them  in  literature  relate 
to  different  forms  of  grave  anaemia.  For  example : 

(1)  Hay  em1  speaks  of   cells  apparently  myelocytes  (he  did 
not  use  Ehrlich's  methods)  in  cases  of  extreme  anaemia. 

(2)  E.  Krebs2  found  them  in  severe  anaemia. 

(3)  Loos s  describes  them  in  the  anaemia  of  hereditary  syphi- 
lis, and  Eille4  finds  them  in  the  anaemia  of  acquired  syphilis. 

(4)  Neusser5  mentions   their  presence   both  in    pernicious 
anaemia  and  in  chlorosis. 

(5)  Hammerschlag6  made  a  similar  observation. 

(6)  Engel 7  noted  their  presence  in  a  case  of  what  he  cau- 
tiously calls  "pseudo-pernicious  anaemia  ,"  and  in  diphtheria. 

(7)  Arnold5  mentions  them. 

(8)  Klein9  gives  a  list  of  various  diseases  (besides  leukaemia) , 
in  which  they  have  been  found,  many  of  which  are  essentially 
anaemic  conditions. 

(9)  Holmes 10    has  found  them  in  phthisis.     I  can  confirm 
this  observation. 

(10)  The  writer  "  found  them  especially  in  the  anaemia  secon- 
dary to  malignant  disease  (see  page  351). 

Besides  these  conditions  the  writer  has  found  them  occa- 
sionally in  almost  all  the  conditions  in  which  leucocytosis  or 
grave  anaemia  is  present — for  example,  in  pneumonia,  malaria, 
sepsis,  peritonitis,  granulating  wounds,  osteomyelitis,  phleb- 
itis, rickets,  Hodgkin's  and  Addison's  disease,  tuberculosis, 
and  other  diseases. 


1  "Du  Sang,"  Paris,  1889,  p.  382. 

2  Inaug.  Dissert.,  Berlin,  1892. 

3  Wien.  klin.  Woch.,  1892,  p.  291. 
*Loc.  cit.,  1893,  No.  9. 

6Zoc.  cit.,  1892,  No.  42. 

6  Berlin  klin.  Woch.,  August  20th,  1894. 

7  Virchow's  Archiv,  vol.  cxxxv. 

8  LOG.  cit.,  vol.  cxl. 

9  Volkmann's  "Sammlung  klin.  Vortrage,"  December,  1893. 

10  New  York  Medical  Record,  September  5th,  1896. 

11  Boston  Medical  and  Surgical  Journal,  loc.  cit. 


122 


CLINICAL   BLOOD    EXAMINATION. 


The  most  curious  example  of  their  occurrence  known  to  me 
is  the  following : 

Mrs.  W—  -  had  been  starving  herself  more  or  less  for  six 
months  from  motives  of  economy.  Two  weeks  before  I  first 
saw  her  she  began  to  suffer  with  cystitis.  From  both  these 
troubles  she  made  a  rapid  recovery,  which  has  persisted  now 
eighteen  months.  There  was  at  the  first  count  a  leucocytosis  of 
15,100;  partly  due  to  cyanosis,  as  she  had  just  been  having  a 
chill.  The  red  cells  were  7,300,000.  Haemoglobin,  eighty -seven 
per  cent.  Differential  counts  were  as  follows : 


Date. 
Number  of  cells  counted. 

May2d 
800. 
Per  cent. 

May  6th 
1,000. 
Per  cent. 

May  7th 
400. 
Per  cent. 

May  8th 
400. 
Per  cent. 

May  13th 
1,000. 
Per  cent. 

"  Polynuclear  neutrophiles".  .  . 
L  y  m  phocy  tcs. 

82.7 
8.6 

82.2 
12.5 

83.6 
9.4 

80.2 
11  3 

68.5 
25  2 

Large  mononuclear 

8.2 

1.5 

2.0 

6  0 

5  2 

Myelocytes                       

.5 

3.5 

4.0 

2  5 

6 

Eosinophiles  .                       ... 

.0 

.3 

1.0 

.0 

5 

What  caused  the  presence  of  myelocytes  I  do  not  know.  At 
that  time  I  had  never  seen  them  in  any  curable  disease  and  was 
alarmed  by  their  appearing,  but  this  case  proves  that  they  are 
not  always  of  any  importance. 

In  a  general  way  their  presence  seems  to  have  about  the  same* 
significance  as  that  of  normoblasts,  but  they  occur  much  more 
frequently.  As  a  rule  I  think  they  indicate  an  acceleration  of 
the  function  of  those  organs  (marrow  ?),  by  which  red  corpus- 
cles and  granular  leucocytes  are  furnished  to  the  blood.  Such 
an  acceleration  may  be  supposed  to  take  place  in  leucocytosis, 
leukaemia,  and  pernicious  anaemia,  which  are  the  chief  condi- 
tions in  which  myelocytes  appear  in  the  blood. 


CHAPTEE  IX. 

GENERAL    PATHOLOGY  OF    THE  BLOOD  AS  REGARDS  HAEMO- 
GLOBIN, FIBRIN,  LIP^EMIA,  MELAN^EMIA  AND 
HEMORRHAGE. 

HEMOGLOBIN. 

As  stated  above,  the  haemoglobin  may  increase  and  diminish 
in  lines  parallel  to  those  of  the  red  cells.  In  that  case  we  sup- 
pose the  amount  of  haemoglobin  per  corpuscle  to  be  normal  and 
the  color  index  or  valeur  globulaire  is  said  to  =  1.  Where  the 
haemoglobin  is  diminished  more  than  the  count  of  corpuscles,  we 
say  that  the  color  index  is  less  than  1.  For  example,  if  a  man 
has  5,000,000  red  cells  per  cubic  millimetre  and  only  50  per  cent 
of  haemoglobin,  we  estimate  the  color  index  by  simply  reducing 
the  count  of  cells  to  a  stated  percentage  (5,000,000  cells  =  100 
per  cent  of  cells)  and  dividing  this  percentage  into  the  haemo- 
globin percentage — i.e.,  TVV  =  0.5  =  the  color  index.  There- 
fore 4,000,000  red  cells  (=  80  per  cent)  with  60  per  cent  of 
haemoglobin  give  a  color  index  of  f^  =  0.75. 

The  color  index  rarely  goes  above  1,  except  in  pernicious 
anaemia  (see  below) .  As  a  rule  when  the  red  cells  are  above  the 
normal  the  haemoglobin  rises  equally,  sometimes  it  lags  behind 
a  little,  but  rarely  if  ever  does  it  rise  higher  than  the  cells. 

In  most  anaemias,  as  has  been  pointed  out,  the  haemoglobin 
suffers  markedly  before  any  considerable  loss  of  red  cells  takes 
place.  In  other  words,  the  corpuscles  seem  to  get  thin  before 
they  die,  and  except  in  malaria,  hemorrhage,  and  a  few  other 
cases  they  are  not  destroyed  while  in  the  full  vigor  of  health.1 

The  loss  of  haemoglobin  is  loss  of  albumin,  the  chief  constit- 
uent of  the  cells,  and  hence  is  usually  loss  of  weight. 

In  general  the  changes  in  the  haemoglobin  are  best  studied  in 
connection  with  changes  in  the  count  of  red  cells,  and  so  far  as 
they  have  not  already  been  mentioned  will  come  in  under  the 
various  special  diseases. 

1  This  is  of  course  not  literal.  There  is  no  reason  to  suppose  that  good- 
sized  corpuscles  get  smaller.  It  is  more  likely  that  a  smaller  generation 
is  sent  out  by  the  blood-making  organs. 


124  CLINICAL   BLOOD   EXAMINATION. 


FIBRIN. 

The  fibrin  network  to  be  seen  in  normal  blood  during  coagu- 
lation (see  page  54)  is  increased  in  a  considerable  number  of 
conditions.  Hayem  has  studied  these  minutely,  and  described 
several  varieties  of  arrangement  of  fibrin  fibres  as  characteristic 
of  special  diseases,  that  is,  he  studied  fibrin  qualitatively  as 
well  as  quantitatively,  and  also  as  regards  the  rapidity  of  its 
formation. 

The  rate  of  fibrin  formation  is  often  not  the  same  as  the  rate 
of  coagulation.  It  is  not  parallel  to  the  number  of  leucocytes  or 
blood  plates,  at  least  not  in  all  cases  (malignant  diseases, 
scurvy). 

In  a  general  way  we  expect  increased  fibrin  in  infectious  and 
inflammatory  diseases,  but  there  are  notable  exceptions  to  this. 
The  greater  the  exudation  and  the  freer  it  is  (in  a  cavity  or 
on  the  surface)  the  thicker  the  fibrin  network,  while  so-called 
interstitial  inflammations  or  such  conditions  as  parenchyma- 
tous  nephritis  show  little  increase  in  fibrin.  The  seat  of  the 
lesions  has  no  considerable  influence,  except  as  it  modifies  the 
nature  of  the  lesion.  An  abscess  in  one  place  has  the  same 
effect  as  an  abscess  elsewhere,  provided  it  is  equally  free  or 
equally  confined,  and  of  the  same  contents. 

Tuberculosis  does  not  increase  fibrin  if  uncomplicated. 
Leucocytosis  and  fibrin  behave  alike  in  many  respects,  espe- 
cially in  relation  to  the  vigor  of  resistance  which  the  individual 
opposes  to  a  given  infection.  When  the  individual  is  so  weak- 
ened that  he  does  not  react  well  against  the  infection,  the  leu- 
cocytes and  fibrin  are  but  slightly  increased,  whereas  in  a  vigor- 
ous individual  the  same  infection  would  have  markedly  increased 
both  fibrin  and  leucocytes.  But  neoplasms  raise  the  count  of 
leucocytes  without  changing  the  amount  of  fibrin. 

In  a  general  way  fibrin  increases  and  decreases  as  fever  does, 
but  often  persists  after  fever  is  gone. 

The  most  marked  fibrin  networks  are  seen  in  pneumonia, 
acute  articular  rheumatism,  suppurative  diseases,  and  in  scurvy. 
In  erysipelas  it  follows  the  leucocytes  (increased  in  severe, 
not  in  mild  cases).  In  the  early  days  of  grippe  it  is  increased. 

The  fever  of  hysteria  or  chlorosis  shows  no  increase  of  fibrin 


LIP^EMIA.  125 

and  post-hemorrhagic  anaemia  with  or  without  fever  shows 
none. 

Fibrin  is  diminished  in  pernicious  anaemia,  not  increased  in 
leukaemia,  typhoid,  malaria,  malignant  disease,  non-suppurative 
diseases  of  liver,  nephritis  (except  interstitial  nephritis,  where 
it  may  be  increased),  heart  disease,  purpura,  haemoglobinuria 
(sometimes  decreased). 

The  most  valuable  point  about  the  fibrin  appears  to  be  the 
absence  of  any  increase  in  malignant  disease,  whereby  a  diag- 
nosis between  the  affection  and  a  suppuration  may  be  helped. 
Otherwise  the  information  given  by  it  is  chiefly  confirmatory  of 
impressions  given  by  other  features  in  blood  examination. 

LIP^MIA. 

The  blood  invariably  contains  small  quantities  of  fat,  espe- 
cially during  digestion  (v.  Jaksch  '). 

In  the  blood  of  persons  suffering  from  a  variety  of  diseases 
such  as  phthisis,  diabetes  mellitus,  obesity,  alcoholism.,  ne- 
phritis, and  in  some  dyspnoeic  conditions,  suppressed  menses, 
pregnancy,  icterus,  typhus,  malaria,  mental  disease,  diseases  of 
the  heart  and  pancreas,  as  well  as  in  health,  fat  is  occasionally 
to  be  seen  in  considerable  quantities.  Grawitz2  finds  that  if 
the  blood  is  collected  in  a  fine  capillary  tube  and  this  is  kept  in 
a  horizontal  position  for  some  time,  fat  rises  to  the  surface  like 
cream,  and  can  be  seen  with  an  oil-immersion  lens  in  the  form 
of  fine  drops.  Gumprecht 3  demonstrated  it  with  osmic  acid, 
which  stains  the  fat  drops  black,  and  proved  them  to  be  fat  by 
dissolving  them  in  ether,  xylol,  etc. 

Lipaemia  has  no  special  significance  so  far  as  is  known,  and 
is  not  characteristic  of  the  diseases  above  mentioned.  Its  cause 
is  unknown. 

[In  almost  any  preparation  of  the  fresh  blood  fat  drops  are 
to  be  seen  unless  the  patient's  skin  is  washed  with  alcohol  be- 
fore puncturing.  Even  with  these  precautions  a  few  drops, 
may  often  be  seen  in  healthy  people's  blood.] 

1  "Klin.  Diagnostik,"  p.  75  (English  translation). 

2  Loc.  ctt.,  p.  180. 

3  Dent.  m«d.  Woch.,  1894,  No.    39. 


126  CLINICAL   BLOOD    EXAMINATION. 


MELAN^MIA. 

In  malaria  the  occurrence  of  a  black  pigment  in  the  leu- 
cocytes which  have  taken  plasmodia  into  themselves,  is  gener- 
ally to  be  seen  during  and  shortly  after  a  paroxysm.  Pigment 
free  in  the  blood  is  only  to  be  seen  at  the  moment  of  seg- 
mentation among  the  new  generation  of  parasites.  The  same 
condition  has  been  observed  in  relapsing  fever  and  in  persons 
; suffering  from  melanotic  malignant  tumors,  the  pigment  being 
always  in  the  white  corpuscles.  Presumably  it  must  at  some 
time  be  free  in  the  plasma,  but  it  is  rarely  if  ever  seen  outside 
the  cells. 

In  Addison's  disease  Tschirkoff '  observed  pigment  in  the 
leucocytes. 

HEMORRHAGE. 

Women  can  stand  a  greater  hemorrhage  and  yet  live  than 
men  can.  Children,  on  the  other  hand,  succumb  to  compara- 
tively slight  hemorrhages  (cf.  Blood  in  Infancy,  page  385).  In- 
dividual differences  make  a  great  difference  in  the  ability  to 
survive  hemorrhage,  and  no  exact  amount  of  blood  can  be 
^stated  as  the  maximum  that  any  one  can  lose  and  yet  survive. 

Changes  in  the  Blood  Eesulling  from  Hemorrhage. 

The  red  cells  and  haemoglobin  of  course  suffer  proportionally 
.at  first;  later  the  haemoglobin  in  the  newly  formed  cells  is 
always  deficient  (see  below). 

The  striking  point  in  the  blood  after  hemorrhage  is  the  evi- 
dence it  gives  us  that  ey^en  before  the  hemorrhage  has  ceased  the 
other  tissues  begin  to  contribute  fluid  to  make  up  the  volume 
upon  which  life  depends.  The  serum  is  markedly  diluted  by 
this  fluid,  but  still  serves  to  give  the  heart  something  to  contract 
on  and  so  prevents  blood  pressure  from  falling  as  fast  as  it 
otherwise  would  do.  Were  it  not  for  such  contributions  from 
neighboring  tissues  the  organism  could  sustain  but  slight 
hemorrhage  without  succumbing  at  once.  We  have  then  after 
.hemorrhage  a  diluted  or  hydrsemic  blood,  even  though  we  do 

it.  f.  klin.  Med.,  vol.  xix.,  1891. 


BLOOD    REGENERATION.  127 

not  assist  the  efforts  of  nature  by  contributing  fluid  by  intra- 
venous or  rectal  injection.  Behier  reports  a  case  due  to  trauma 
in  which  the  count  was  only  688,000  per  cubic  millimetre. 

Coagulation  increases  in  rapidity  the  more  blood  is  lost,  so 
that  after  severe  hemorrhage  it  takes  place  almost  instantly. 

BLOOD  [REGENERATION. 

The  regeneration  of  the  blood  after  hemorrhage  may  be  taken 
as  typical  of  the  same  process  in  anaemia  from  other  causes. 

The  length  of  time  needed  for  full  restoration  to  normal 
depends  not  merely  on  the  (a)  amount  of  blood  lost,  but  also  on 
the  (b)  age  and  nutrition  of  the  patient  as  well  as  upon  (c)  the 
methods  of  treatment  carried  out  and  the  existence  of  (d)  other 
disease  (typhoid,  malignant  disease,  phthisis,  etc.). 

Allowing  for  these  other  conditions  we  may  say  that,  other 
things  being  favorable,  the  loss  of 

I.  Less  than         1  per  cent  of  the  blood  mass  is  made  up  in   2  to  5  days. 
II.  From        1  to  3  "          "  "         5  rt  14    " 

III.      «  3  "  4        "  "  "          "  "        14  «  30    " 

The  last  amount  means  a  very  severe  hemorrhage.  Few 
surgical  operations  involve  the  loss  of  over  three  per  cent,  and 
after  such  accordingly  we  expect  the  blood  to  be  normal  again 
in  two  weeks,  provided  the  individual  is  otherwise  sound  (see 
Malignant  Disease,  page  335) . 

Young,  well-nourished  persons  are  of  course  quicker  in  mak- 
ing up  losses  than  the  old  and  weak. 

Blood  Condition  During  Regeneration. 

1.  Red  Cells. — (A)  As  previously  mentioned,  the  haemoglo- 
bin becomes  relatively  low  as  soon  as  the  regenerative  process 
is  well  established,  and  as  recoverj^  progresses  the  red  cells  are 
almost  always  normal  in  numbers  for  some  time  before  the  stat- 
ure, weight,  and  color  of  the  individual  cells  is  what  it  should 
be.  A  color  index  of  0.50-0.60  is  not  unusual— in  short,  what 
some  call  a  "  chlorotic"  condition  of  the  blood. 

(B)  Qualitative  changes  are  those  already  described  on  page 
72,  namely :  (a)  Deformities  in  size  and  shape  with  an  average 
diminution  in  size;  (b)  polychromatophilic  cells;  and  (c)  nucle- 


128  CLINICAL   BLOOD    EXAMINATION. 

ated  corpuscles.     These  latter  are  almost  exclusively  of  the  nor- 
moblast  type,  but  an  occasional  megaloblast  has  been  observed. 

Blood  Crises. — Yon  Noorden  was  the  first  to  notice  that  in 
some  cases  nucleated  corpuscles  are  to  be  found  in  the  circu- 
lation in  great  numbers  for  a  few  hours  only,  the  blood  examina- 
tion both  before  and  after  showing  few  or  none  at  all.  The 
name  of  "  blood  crisis"  has  been  given  to  these  sudden  outpour- 
ings of  nucleated  red  cells ;  they  are  to  be  observed  during  re- 
covery from  various  forms  of  anaemia. 

2.  Willie  Cells. — Immediately  after  a  loss  of  blood  we  can 
usually  find  a  decided  leucocytosis  despite  the  dilution  of  the 
blood  (see  above,  Post-hemorrhagic  Leucocytosis). 

This  leucocytosis  is  in  no  way  different  from  those  occurring 
from  other  causes.  The  percentage  of  polymorphonuclear  cells 
is  usually  increased,  and  the  eosinophiles  often  disappear.  As 
pointed  out  by  Stengel  we  may  have  a  lymphocytosis  after 
hemorrhage.  A  case  of  anaemia  from  bleeding  piles,  in  which 
the  red  cells  were  2,723,000  and  the  haemoglobin  35  per  cent, 
showed  in  a  total  leucocyte  count  of  4,200,  69  per  cent  of  small 
lymphocytes  and  only  28  per  cent  of  polymorphonuclear  cells. 
Leucocytosis  if  present  is  rarely  very  high,  seldom  reaching  over 
30,000.  It  is  not  invariably  present,  or  if  present  sometimes  is 
of  very  short  duration.  Thus  in  a  patieut  whose  red  cells  were 
reduced  to  3,200,000  by  a  profuse  uterine  hemorrhage  the 
white  cells  counted  next  day  were  only  8,000;  while  in  the  next 
bed  of  the  hospital  was  a  woman  crushed  in  a  railroad  accident 
whose  red  cells  were  1,280,000,  and  the  white  cells  28,000,  the 
usual  state  of  things. 

The  leucocytes  may  be  increased  even  by  a  cerebral  hemor- 
rhage which  is  not  large  enough  considerably  to  affect  the  red 
cells  in  most  cases.  Ten  apoplectic  cases  (with  autopsy)  ob- 
served at  the  Massachusetts  Hospital  showed  such  counts  as 
the  following : 

1.  Eed  cells  5,512,000,  white  cells  25,000,  Hb.  85  per  cent. 

2.  Bed  cells  5,560,000,  white  cells  15,600,  Hb.  90  per  cent. 
Whether  the  leucocytes  are  here  affected  by  any  influence 

other  than  that  of  hemorrhage  I  do  not  know. 

The  effect  of  transfusion  (intravenous  saline  solution)  is  ap- 
parently at  first  to  increase  the  leucocytosis. 

D ,  a  patient  with  traumatic  rupture  of  the  urethra,  had 


BLOOD   REGENERATION.  129 

had  severe  hemorrhage  for  forty-eight  hours  before  it  was 
checked  at  1  P.M.,  November  1st,  1895.  At  4  P.M.,  his  pulse 
being  165,  the  count  showed:  red  cells,  3,304,000;  white  cells, 
10,400.  He  was  at  once  given  a  pint  of  sterilized  normal  salt 
solution  by  intravenous  injection  under  the  strictest  asepsis. 
Ten  minutes  after  the  transfusion  the  leucocytes  numbered 
32,400.  One  hour  later  they  were  24,700,  and  the  red  cells 
3,632,000.  Four  hours  later  leucocytes,  31,900;  red  cells, 
3,046,000.  The  later  counts  were  as  follows : 

Red  cells.  White  cells. 

November    2d  :  good  pulse 3, 608, 000  34, 600 

3d  (5  P.  M. )  :  good  pulse 2, 944, 000  30, 200 

3d  (4  p.  M. )  :  good  pulse 2, 928, 000  15, 800 

13th 3,360,000  16,600 

A  good  recovery  was  made. 


IMPORTANCE  FOB  SURGERY  OF  BLOOD  COUNTING  AFTER 
HEMORRHAGE. 

Mikulicz,  who  as  a  surgeon  should  speak  with  authority  and 
who  always  takes  account  of  the  condition  of  the  blood  in  his 
cases,  lays  down  (following  Laker)  the  following  rule:  Never 
operate  on  any  case  when  the  Immoglobin  is  below  thirty  per  cent. 
The  question  of  operating  at  once  or  waiting  for  recovery  from 
"shock,"  is  a  very  common  one  in  the  accident  rooms  of  any 
hospital  and  is  generally  settled  on  general  impressions  of  the 
patient's  vigor.  We  know,  say,  that  he  has  lost  blood,  but  we 
have  no  way  of  ascertaining  how  much.  If  his  "  shock"  is  due 
to  hemorrhage  he  may  need  transfusion ;  if  it  is  due  to  cerebral 
concussion  or  compression,  the  transfusion  will  do  more  harm 
than  good.  The  blood  count  can  settle  these  questions,  and 
could  reveal  much  which  is  now  obscure,  if  it  were  more  fre- 
quently employed  in  surgical  cases  and  a  standard  like  that  of 
Mikulicz  worked  out. 

In  cases  of  suspected  ruptured  tube  in  extra-uterine  preg- 
nancy, the  question  of  whether  the  patient  is  suffering  from  in- 
ternal concealed  hemorrhage  can  be  settled  in  many  cases  by 
the  blood  count,  which  will  show  a  decided  loss  of  red  cells  if 
9 


130  CLINICAL   BLOOD   EXAMINATION. 

the  hemorrhage  is  large,  and  thereby  distinguish  the  condition 
from  peritonitis,  obstruction,  or  strangulated  hernia,  none  of 
which  affects  the  red  cells.  Any  other  concealed  hemorrhage,  as 
for  instance  from  ruptured  kidney  or  spleen  or  liver,  may  be 
indicated  by  the  blood  count  when  by  other  physical  signs  the 
diagnosis  might  be  very  difficult. 

Summary. 

The  blood  count  is  of  importance  after  cases  of  supposed 
hemorrhage. 

1.  To  ascertain  whether  such  has  taken  place. 

2.  Its  extent. 

3.  Whether  operation  is  to  be  immediate  or  not. 

4.  Whether  transfusion  is  indicated. 

5.  How  soon  the  patient  has  got  back  enough  blood  to  make 
operation  worth  while. 

CHRONIC  HEMORRHAGE. 

Piles,  uterine  disease,  haemophilia,  purpura,  and  other  causes 
may  produce  a  long-standing  drain  on  the  blood. 

Some  patients  apparently  can  lose  a  little  blood  almost  daily 
for  years  without  acquiring  any  severe  anaemia,  and  if  the  indi- 
vidual is  otherwise  sound  and  does  not  suffer  from  an  underly- 
ing disease  like  phthisis,  cancer,  or  nephritis,  he  can  probably 
go  on  for  a  long  time  without  showing  any  bad  effects  from  the 
repeated  small  hemorrhages.  How  much  he  can  stand  we  have 
no  way  of  judging,  for  we  cannot  measure  the  amount  of  blood 
lost.  When,  however,  such  small  repeated  losses  do  produce  an 
anaemia,  regeneration  is  apt  to  be  much  slower  than  after  a 
single  large  hemorrhage.  The  longer  the  drain  has  been  going 
on  the  poorer  the  chance  for  recovery,  and  the  slower  the  latter 
will  be  if  it  does  take  place. 

Gain  in  body  weight  does  not  always  mean  gain  in  corpuscle 
substance  as  well  (see  Malignant  Disease,  page  335) . 


BOOK  II. 


SPECIAL  PATHOLOGY  OF  THE  BLOOD. 


PART  I. 

DISEASES  OF  THE  BLOOD. 


CHAPTEE  I. 

THE  PRIMARY   ANAEMIAS. 

1.  THE  BLOOD  IN  PERNICIOUS  ANEMIA. 

THE  definition  of  the  disease  has  been  sufficiently  explained 
before  (see  page  84)  and  we  can  proceed  at  once  to  the  descrip- 
tion of  the  blood. 

1.  Gross  appearances. 

(a)  The  drop  as  it  emerges  from  the  puncture  is  often  exces- 
sively pale  and  watery,  but  not  more  so  than  may  occasionally 
be  seen  in  secondary  anaemia  or  chlorosis.  Sometimes  it  is  not 
nearly  so  pale  as  in  other  cases  with  equally  low  counts,  a  fact 
which  may  be  due  to  the  increased  color  index  sometimes  present 
(see  below).  In  one  case  (color  index  1.2)  I  have  seen  the 
blood  as  red  as  normal. 

Another  appearance,  which  I  have  frequently  observed  in 
this  and  other  anaemias,  is  an  uneven,  streaked  color  in  tho 
drop,  as  if  the  cells  were  unequally  divided  in  the  plasma. 

(&)  As  striking  as  the  color  of  the  drop  is  its  great  fluidity ; 
the  rapidity  with  which  it  slips  off  the  ear  or  finger  often  makes 
it  difficult  to  suck  it  up  in  time.  It  is  usually  very  slow  in 
coagulating. 

2.  The  fresh  specimen  in  most  cases  shows  no  rouleaux  forma- 
tion, a  diminution  in  blood  plates  and  fibrin,  and  usually  great 
variations  in  the  size  and  shape  of  the  corpuscles  with  a  ten- 
dency to  an  oval  shape  and  an  increase  in  the  average  diameter. 
Not  infrequently  the  deformed  corpuscle  shows  active  pseudo- 
amoeboid  motions  of  its  projecting  points  or  of  the  cell  as  a 
whole.     The  great  lack  both  of  red  and  white  cells  is  noticeable 
even  in  the  fresh  specimen. 


134 


SPECIAL   PATHOLOGY    OF   THE   BLOOD. 


Red  Cells  and  Haemoglobin. 

(a)  Quantitative  changes  (see  Table  I.).  The  average  count  of 
red  cells  in  the  sixty-eight  cases  of  my  table  is  about  1,200,000, 
which  may  be  taken  as  the  average  count  in  patients  seen  at  the 
stage  of  the  disease  at  which  they  feel  sick  enough  to  seek  medi- 
cal advice.1  We  very  rarely  get  an  opportunity  to  examine  the 
blood  in  the  early  stages  of  the  disease,  so  that  we  have  to  judge 
of  them  chiefly  from  the  evidence  given  during  the  remission  so 
commonly  observed.  In  the  relapse  following  such  a  remission 
the  blood  count  may  fall  from  5,000,000  to  1,000,000  in  a  period 
of  from  six  weeks  to  six  months.  In  the  later  stages  of  the  dis- 
ease 500,000  red  cells  per  cubic  millimetre  is  not  rare,  and  if  the 
diminution  has  been  gradual,  the  patient  may  be  up  and  about 
and  able  to  do  light  work  with  a  count  no  greater  than  this.  I 
had  an  opportunity  to  observe  such  a  case  in  the  wards  of  Dr. 
"F.  C.  Shattuck  at  the  Massachusetts  General  Hospital  five 
years  ago,  where  for  several  weeks  the  blood  count  remained  at 
or  near  500,000,  yet  the  patient  was  outdoors  daily,  read  the 
papers,  and  seemed  perfectly  comfortable.  Evidently  it  is  not 
the  anaemia  itself  which  kills  the  patient. 

The  lowest  count  on  record  is  that  reported  by  Quincke — 
143,000  per  cubic  millimetre. 

TABLE  I. 


(a)  FIRST 

COUNT. 

(6)  HlGHES 

T  COUNT. 

(c)  LOWES! 

c1  COUNT. 

Total 

1 

Red  cells. 

Per  cent 
haemo- 
globin. 

Red  cells. 

Per  cent 
haemo- 
globin. 

Red  cells. 

Per  cent 
haemo- 
globin. 

number  of 
exam- 
inations. 

1 

2 
3 
4 
5 

450,000 
490,000 
503,000 
510,000 
600,000 

10 

? 

10 
20 
24 

658,  000 
490,000 
522,000 
680,000 

18 

? 
18 

? 

363,000 
410,000 
368,  000 
510,  000 

10 

9 

10 
20 

6 
2 
6 
3 
1 

6 

7 
8 
9 
10 
11 
12 
13 

630,000 
670,000 
680,000 
694,000 
735,000 
784,  000 
842,000 
896,000 

V 
20 
20 

? 

14 
? 
18 

658,000 
670,000 
680,000 
2,654,000 
1,500,000 
784,000 
842,  000 
896,000 

? 
'26' 

v 
14 

? 
18 

450,000 
670,  000 
680,000 
694,000 
730,000 
784,000 
842,000 
430,  000 

? 

'26 
20 
? 
14 
? 
6 

13 
1 
1 
8 
3 
1 
1 
3 

lCf.   Schaumann  :  Out  of  his  38  cases,    1   was  over  2,000,000;   26  be- 
tween 1,000,000  and  2,000,000  ;  11  below  1,000,000  ;  average  1,290,000. 


THE   BLOOD   IN   PERNICIOUS   ANJEMIA. 


135 


TABLE  I .  —  ( Continued) . 


6 
fc 

(a)  FIRST  COUNT. 

(6)  HIGHEST  COUNT. 

(c)  LOWEST  COUNT. 

Total 
number  of 
exam- 
inations. 

Red  cells. 

Per  cent 
haemo- 
globin. 

Red  cells. 

Per  cent 
haemo- 
globin. 

Red  cells. 

Per  cent 
haemo- 
globin. 

14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
35 
36 
37 
38 
39 
40 
41 
42 
43 
44 
45 
46 
47 
48 
49 
50 
51 
52 
53 
54 
55 
56 
57 
58 
59 
60 
61 
62 

896,  000 
962,000 
963,  000 
984,  000 
988,  000 
992,593 
1,018,000 
1,096,400 
1,064,000 
1,060,524 
1,092,000 
1,111,000 
1,113,000 
1,126,000 
1,137,000 
1,140,000 
1,150,000 
1,150,000 
1,176,000 
1,200,000 
1,226,284 
1,270,000 
1,280,000 
1,288,000 
1,289,000 
1,296,000 
1,300,000 
1,336,000 
1,344,000 
f,  364,  000 
1,493,000 
1,498,000 
1,500,000 
1,516,000 
1,582,000 
1,583,000 
1,600,000 
1,627,000 
1,632,000 
1,755,000 
1,768,000 
1,800,000 
1,800,000 
1,800,000 
1,819,000 
1,872,000 
1,884,000 
1,920,900 
1,929,000 

17 
15 
38 
28 
? 
34 
20 
12 
23 
35 
25 
? 
18 
? 
*  20 
20 
? 
30 
29 
15 
25 
16 
24 
? 
32 
25 
28 
28 
23 
35 
32 
20-30 
35 
35 
20 
20 
25 
? 
28 
20 
? 
28 
25 
30 
34 
25 

'33' 
38 

3,800,000 
1,028,080 

70 
15 

608,000 
962,  000 

15 
15 

20 
3 
1 
3 
1 
2 
1 
4 
5 
1 
5 
3 
8 
2 
4 
3 
16 
1 
1 
1 
12 
2 
16 
3 
5 
3 
2 
3 
3 
1 
2 
1 
8 
3 
12 
4 
10 
1 
7 
2 
6 
5 
1 
3 

3 
4 
4 
1 

1,080,000 

? 

992,593 

34 

1,096,400 
1,420,000 

1,150,000 
1,111,000 
2,820,000 
1,126,000 
1,137,000 
1,140,000 
2,802,000 

13 
25 

'39' 

? 
? 
? 
20 
20 

624,000 
1,064,000 

13 
23 

? 
? 
? 
15 
25 

893,000 
756,  000 
1,038,000 
1,100,000 
550,000 
622,160 
1,150,000 

4,450,000 
2,700,000 
1,328,000 
1,910,000 
1,628,000 
1,296,000 
1,300,000 
1,336,000 
1,344,000 

65 
30 
29 

? 

34 
25 

28 
28 
23 

762,000 

"664,000 
1,288,000 
1,121,000 
1,248,000 
970,000 
956,000 
758,000 

? 
'22" 

'34' 
25 
30 
20 
17 

1,500,000 

? 

3,700,000 
1,916,000 
4,760,000 
1,768,000 
4,032,000 

53 
35 
52 

40 

80 

1,460,000 
1,516,000 
1,624,000 
1,500,000 
1,288,000 

30 
35 
30 
20 
23 

1,632,000 
1,755,000 
2,458,000 
2,868,000 

28 
20 
? 
41 

'36' 
25 
'35' 

1,180,000 
1,117,000 
1,768,000 
1,508,000 

30 
20 
? 
31 

1,800,000 

1,872,000 
1,889,314 
1,930,000 

1,768,000 

1,144,000 
1,330,000 
1,600,000 

22 
30 
'28* 

136 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 
TABLE  I.— (Continued). 


6 
& 

(a)  FIRST  COUNT. 

(6)  HIGHEST  COUNT. 

(c)  LOWEST  COUNT. 

Total 
number  of 
exam- 
inations. 

Red  cells. 

Per  cent 
haemo- 
globin. 

Red  cells. 

Per  cent, 
haemo- 
globin. 

Red  cells. 

Per  cent 
haemo- 
globin. 

63 
64 
65 
66 
67 
68 

1,946,000 
1,984.000 
2,000,000 
2,080,000 
2,076,000 
2,  524,  000 
Average= 
1,200,000 

40 
39 
20 
25 
15 
26 

26 

39 
20 
70 
45 
26 

3 
3 

2 
9 
10 
5 

293 

?e  =  4  + 

1,984,000 
2,000,000 
5,056,000 
4,500,000 
2,524,000 

598,000 
1,200,000 
1,632,000 
1,384,000 
1,280,000 

15 
20 

50(?) 
10 
13 

Averai 

The  great  but  temporary  improvements  above  alluded  to, 
followed  by  relapse,  occur  either  with  or  without  treatment. 
In  the  course  of  a  few  months  the  count  of  red  cells  may  rise 


w 

'.4000000 

-"Haemoglobin           vn/\rvi    j.  . 

t, 

70 

\ 

N 

/ 

9 

."X 

.. 

60 

3000000 

V 

) 

" 

" 

V 

•\ 

50' 

i  r  / 

\ 

•-V' 

J 

40; 

zoooooo 

_5J 

\ 

j 

\ 

», 

3$ 

I 

2 

\  • 

Vf 

f 

r 

! 

*• 

20/ 

1000000 

N 

- 

v* 

10; 

V 

Red  Cells 
Haem 

4500000 


CHART  ]i 


^ 

3000000 

50'/u 

,2,000000  40% 
30% 

.1000000  ao% 
10% 


1* 

/ 

_7 

y 

r- 

^ 

> 

* 

/ 

\ 

.• 

2 

3 

... 

** 

•••. 

.. 

^TT^edCeUs 

3000000  60% 
Z5  ooooo  sol 

ZQOOOOO  40} 
1500000  30f 
1000000  Ml 
500000   10/v 

CHART  m              j 

\ 

^ 

... 

^^ 

^; 

- 

.,• 

"«.. 

"^ 

^ 

\ 

^ 

s 

\ 

\ 

tHE  BLOOD   IN  PERNICIOUS  ANEMIA.  137 

to  normal,  the  nucleated  corpuscles  (see  below)  disappear,  and 
the  patient  is  apparently  restored  to  health  and  goes  to  work 
with  a  laugh  at  the  doctor.  I  have  followed  one  case  through 
five  such  relapses  in  a  period  of  three  years  before  the  fatal 
issue  came.  Frequently  the  patient  feels  so  well  during  one  of 
these  remissions  that  he  goes  to  work  and  is  lost  sight  of,  and, 
under  such  conditions,  the  incautious  are  apt  to  report  "cure." 

The  accompanying  charts  l  show  the  three  types  usually  met 
with ;  No.  II.  being,  of  course,  only  a  fragment  of  a  case  similar 
to  No.  I.,  while  the  steady  progression  of  No.  III.  may  have 
been  preceded  by  a  rise  from  a  former  downfall,  though  no  such 
history  was  obtained. 

Looking  over  a  considerable  number  of  cases,  one  can 
hardly  help  being  struck  with  the  tendency  of  the  count  to 
remain  near  the  figure  1,000,000.  Cases  rarely  remain  sta- 
tionary at,  say,  2,000,000,  and  often  die  without  sinking  be- 
low 1,000,000.  It  seems  as  if  some  self-applying  mechanism 
tended  to  arrest  the  destruction  of  corpuscles  at  or  near  this 
point  (see  Table  I.). 

In  counting  the  red  cells  some  difficulty  and  error  may  result 
from 'the  very  small  size  of  some  of  the  cells.  It  is  especially 
important  that  the  diluting  solution  should  be  clean  and  freshly 
made,  else  without  the  aid  of  a  stain  it  may  be  hard  to  distin- 
guish the  dwarf  cells  or  microcytes  from  bits  of  extraneous  sub- 
stance. 

Quantitative  Changes. 

White  Corpuscles  (see  Table  II.).— The  rule  is  a  very  consid- 
erable diminution  in  the  number  of  leucocytes.  Thus  of  sixty 
cases  which  I  have  examined  forty -two  were  under  5,000,  the 
average  of  all  being  3,800. 

[I  have  excluded  from  this  series  counts  made  immediately 
after  hemorrhages  and  counts  in  infants.  The  latter  are  very 
apt  to  show  a  leucocytosis  in  connection  with  any  form  of 
anaemia.] 

As  the  disease  progresses  the  leucocytes  fall  even  more 
rapidly  than  the  red  cells,  and  counts  as  low  as  500  white  cells 
per  cubic  millimetre  are  not  uncommon. 

1  The  number  of  perpendicular  lines  represents  the  number  of  weeks. 


138 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


Leucocytosis  when  present  in  the  blood  of  adult  cases  is 
always  due  to  some  complication  like  hemorrhage  or  suppura- 
tion. 

TABLE  II. — WHITE  CELLS — FIRST  EXAMINATION. 


No. 

White  cells. 

No. 

White  cells. 

No. 

White  cells. 

1              .    .  . 

400 
500 
800 
1,000 
1,000 
1,000 
1,500 
1,600 
1,800 
2,000 
2,000 
2,000 
2,000 
2,000 
2,300 
2,600 
2,800 
2,800 
2,800 
2,800 

21 

2,900 
3,000 
3,000 
3,200 
3,200 
3,300 
3,400 
3,500 
3,600 
3,700 
3,704 
4,000 
4,000 
4,000 
4,000 
4,200 
4,300 
4,400 
4,500 
4,720 

41 

4,828 
4,900 
5,000 
5,200 
5,300 
5,500 
5,600 
6,000 
6,000 
6,000 
6,400 
6,500 
7,000 
7,  200 
7,500 
7,600 
9,000 
9,600 
10,000 
10,100 
=  3,8004- 

2  

22      

42 

3  

23  

43 

4  

24  

44    

5 

25 

45 

6 

26 

46 

7     

27  

28 

47 

8       

48 

9  

29  
30 

49 

10  

50 

11  

31  
32    

51 

12  

52 

13  

33    

53        

14 

34 

54 

15.. 
16     

35  
36 

55  
56  
57 

17  

37 

18  

38  . 

58 

19  

39  

59 

20 

40 

60  
Average 

As  mentioned  above,  the  blood  plates  and  fibrin  are  much 
diminished. 

In  four  cases  in  which  Dr.  Lindstrom,  of  Boston,  was  kind 
enough  to  give  massage,  we  were  unable  to  see  the  slightest  gain 
either  in  corpuscles  or  haemoglobin,  such  as  can  be  produced 
temporarily  in  most  healthy  persons.  The  observations  of  J. 
Mitchell  on  this  point  we  were  unable  to  confirm. 

Haemoglobin. 

.  The  great  majority  of  cases  of  pernicious  anaemia  have  a 
relatively  high  percentage  of  haemoglobin  (e.g.,  1,000,000  red 
cells  and  35  per  cent,  of  haemoglobin,  or  a  color  index  of  1.75). 
In  some  cases  this  is  not  so,  and  in  others  we  cannot  tell 
whether  it  is  so  or  not,  owing  to  the  unreliability  of  the  v. 
Fleischl  instrument  when  used  for  very  low  haemoglobin  per- 
centages. 

Of  the  50  cases  in  the  series  on  page  134,  in  which  the  haemo- 


THE   BLOOD   IN   PERNICIOUS   ANAEMIA.  139 

globin  was  tested,  a  color  index  of  over  1  was  apparently 
present  in  29,  or  58  per  cent,  and  a  color  index  of  less  than  1 
in  21,  or  42  per  cent,  of  the  cases.  How  many  of  these  haemo- 
globin estimations  may  have  been  wrong  I  cannot  say. 

From  the  frequency  with  which  we  find  the  corpuscles  well 
stained  and  larger  than  normal  in  pernicious  anaemia  (see  below), 
we  should  expect  that  the  haemoglobin  would  be  relatively  high, 
and  in  a  larger  percentage  of  cases  than  the  v.  Fleischl  instru- 
ment indicated. 

An  increased  color  index  is  probably  a  bad  prognostic  sign. 
In  the  remissions  of  the  disease  when  the  cells  are  increasing 
fast,  the  haemoglobin  lags  behind  and  the  color  index  is  low. 
As  the  relapse  follows,  the  color  index  in  many  cases  progres- 
sively increases.  Cases  ivhose  color  index  is  low  and  in  which 
the  average  diameter  of  the  red  cells  is  normal  are  apt  to  be 
gaining  at  that  time,  while  those  with  high  color  index  are  apt 
to  be  losing  at  that  time. 

The  average  color  index  in  the  cases  in  which  the  haemo- 
globin and  red  cells  were  both  tested  was  1.04,  the  average 
percentage  of  haemoglobin  being  26  and  of  corpuscles  24 
(-1,200,000). 

QUALITATIVE  CHANGES. 
1.  Red  Corpuscles. 

(a)  Increase  in  the  average  diameter  of  the  cells  is  a  very 
constant  and  striking  feature  of  the  stained  specimens  in  this 
disease.     In  no  other  disease  do  so  large  cells  or  so  many  of 
them  occur. 

Out  of  forty -eight  cases  in  which  I  have  looked  for  this 
point,  forty-one  showed  the  increase,  as  far  as  could  be  judged 
without  actually  measuring  any  large  number  of  cells.  This 
does  not  mean  that  every  cell  is  larger  than  normal,  but  that 
those  larger  than  normal  outnumber  those  undersized;  the 
"macrocytes"  are  more  numerous  than  the  "microcytes."  Oc- 
casionally we  see  cells  over  20  v  in  diameter,  some  with  nuclei, 
some  without. 

(b)  Deformities  in  Shape. — The  eye  soon  gets  used  to  the 
shapes  assumed  by  the  necrobiotic  corpuscles  and  learns  to  dis- 
tinguish them  from  the  distortions  due  to  technique  or  to  crena- 


140 


SPECIAL   PATHOLOGY   OF   THE   BLOOD, 


tion.  Most  of  them  fall  under  one  or  another  of  the  types  shown 
in  Plate  IV.  Litten  has  laid  particular  stress  on  the  horseshoe 
forms,  and  thinks  them  peculiar  to  pernicious  anaemia.  The 
battledore  and  sausage-shaped  forms  are  very  common.  In 
one  case  I  found  all  the  red  cells  of  the  latter  shape,  so  that  they 
looked  at  first  sight  like  a  lot  of  gigantic  bacilli.  That  this  ap- 
pearance was  not  due  to  the  technique1"  (as  I  had  at  first  sup- 
posed) is  probable  from  the  fact  that  the  rod-shaped  cells  did 
not  point  all  in  one  direction  as  they  would  have  done  if  pulled 
out  of  shape  by  the  process  of  spreading  (see  Fig.  30) .  This  ap- 


PIG.  30.— Elongated  or  Oval  Corpuscles  in  Pernicious  Anaemia,  resembling  the  blood  of 

lower  animals. 

pearance  is  only  an  exaggeration  of  what  may  be  seen  in  most 
severe  anaemias,  namely,  a  tendency  toward  an  oval  shape  like 
that  of  amphibian  corpuscles.  This  is  usually  true  of  those 
cells  (in  pernicious  cases)  which  are  not  more  violently  deformed. 
Occasionally  we  see  cases  with  no  considerable  deformities 
whatever  in  the  red  cells.  In  nine  cases  out  of  sixty  in  which 

1  Some  writers  advise  the  use  of  less  heat  than  usual  in  dealing  with 
cover-glass  specimens  of  pernicious  anaemia.  I  have  not  found  this  so, 
and  heat  as  usual  up  to  150°  C.  and  then  stop. 


THE   BLOOD   IN    PERNICIOUS   ANAEMIA.  141 

this  point  was  observed,  little  or  no  deformity  was  noted.  I 
cannot  make  out  that  such  cases  have  any  better  or  worse  prog- 
nosis than  others.  I  have  never  seen  cases  whose  red  cells  were 
all  undersized,  but  a  normal  average  diameter  was  present  in 
somewhat  under  one-quarter  of  the  cases  in  which  I  have  looked 
out  for  this  point. 

(c)  Staining  Properties  of  the  Red  Cells. — The  white  spots  or 
streaks  described  by  Maragliano,  Hayem3  and  others  are  very 
often  seen  in  the  red  cells  of  pernicious  anaemia  despite  good 
technique.  Some  corpuscles  are  so  pale  in  the  centre  that  we 
see  only  the  narrow  ring  of  stained  protoplasm  at  the  periph- 
ery, a  mere  shell.  Others  are  swollen  up  so  as  to  show  no  sign 
of  central  biconcavity,  and  stain  deeply  and  evenly  all  over. 

More  common  than  in  any  other  form  of  anaemia  are  the 
polychromatophiiic  red  corpuscles  (see  Plate  IV.)  which  with 
the  Ehrlich-Biondi  mixture  stain  brownish,  purple,  or  gray, 
either  as  a  whole  or  in  parts.  In  the  nucleated  red  cells  the  pro- 
toplasm is  very  apt  to  show  this  change,  so  that  it  is  often  diffi- 
cult to  distinguish  them  from  lymphocytes.  In  difficult  cases 
we  have  sometimes  to  fall  back  upon  the  appearances  of  the 
edge  or  periphery,  which  in  most  red  corpuscles  shows  some 
thin  place  or  crinkle  characteristic  of  a  flat  cell,  while  the  lym- 
phocyte gives  us  the  more  solid-looking  outline  of  the  spherical 
cell. 

All  these  microchemical  changes  can  be  better  brought  out 
with  haematoxylon-eosin  or  eosin-methyl-blue  stains,  but  all 
that  is  needed  for  clinical  purposes  can  be  made  out  with  the 
ordinary  Ehrlich-Biondi  mixture. 

Nucleated  Red  Corpuscles. 

Nothing  further  needs  to  be  said  in  description  of  these  forms 
(see  above,  pages  89-94).  We  have  no  exact  method  of  estimating 
the  number  of  nucleated  cells  either  in  relation  to  the  whole  num- 
ber of  red  cells  or  in  a  cubic  millimetre.  All  we  can  do  is  to  note 
the  number  seen  in  such  an  area  of  a  cover-glass  specimen  as  is 
covered  while  counting  a  given  number  of  white  cells,  say  1,000. 
Knowing  the  ratio  of  red  to  white  corpuscles,  we  can  calculate 
from  this  number  of  nucleated  red  cells  their  approximate  re- 
lation to  the  whole  number  of  red  cells. 

Thus  if  the  ratio  of  white  to  red  be  1:1000  (1,000,000  red 
and  1,000  white)  and  we  have  seen  two  nucleated  red  corpuscles 


142  THE    BLOOD    IN   PERNICIOUS   ANJEMIA. 

while  making  a  differential  count  of  1,000  white  cells,  the  total 
number  of  red  cells  passed  over  must  be  approximately  1,000,- 
000  and  the  number  of  nucleated  corpuscles  about  two  in  1,000,- 
000  red  cells  or  two  in  a  cubic  millimetre.  Of  course  where 
leucocytosis  is  present  and  the  ratio  is  raised — say  to  1 : 150 
(10,000  white  and  1,500,000  red)— finding  two  nucleated  rec! 
cells  while  counting  1,000  white  would  mean  that  there  were 
two  nucleated  cells  in  every  150,000  non-nucleated,  or  twenty 
in  a  cubic  millimetre  (or  in  1,500,000  non-nucleated  cells). 

Such  calculations  are  inaccurate  because  we  are  never  sure 
that  the  red  cells  and  white  cells  are  distributed  in  the  dried  speci- 
men exactly  as  they  are  in  the  blood.  Part  of  the  leucocytes 
may  be  accumulated  at  the  edges  of  the  cover-glass  so  that  the 
ratio  in  the  middle  may  be  different  from  that  in  the  circulating 
blood. 

Nevertheless  we  can  get  some  idea  of  how  plentiful  the  nu- 
cleated corpuscles  are,  and  as  their  significance  in  prognosis 
depends  far  more  on  their  kind  than  on  their  number,  greater 
accuracy  as  to  the  latter  is  not  at  present  important.  For  in- 
stances, two  megaloblasts  per  cubic  millimetre  mean  a  worse 
prognosis  than  twenty  normoblasts,  provided  there  are  no  other 
kinds  present  in  either  case.  It  is  the  ratio  of  megaloblasts  to 
normoblasts  and  not  the  absolute  number  of  each,  that  is  of  im- 
portance. 

In  all  of  the  sixty  cases  of  pernicious  anaemia  in  which  I 
have  examined  the  blood,  the  number  of  megaloblasts  has  ex- 
ceeded the  number  of  normoblasts,  and  as  the  cases  grew  worse 
the  megaloblasts  grew  relatively  more  numerous  (often  abso- 
lutely as  well).  Further,  in  several  hundred  cases  of  severe 
secondary  anaemia  I  have  never  yet  seen  the  number  of  megalo- 
blasts exceed  the  number  of  normoblasts. 

The  range  of  variation  in  the  number  of  nucleated  cells  pres- 
ent has  extended  in  my  series  from  6  per  cubic  millimetre  to 
7,100  per  cubic  millimetre  (see  Table  III.).  The  calculation  can 
be  made  by  using  the  following  formula. 

Let  n  =  the  number  of  white  cells  counted  (by  differential  count). 
"    m  =      "  "      nucleated  red  cells  seen  while  counting  these. 

"    p  =:      "  "      white  cells  per  cubic  millimetre  (Thoma-Zeiss). 

p  x  —  =  x  =  number  of  nucleated  red  cells  per  cubic  millimetre. 
The  search  for  nucleated  corpuscles  in  pernicious  anaemia 


THE   BLOOD    IN   PERNICIOUS   ANEMIA. 


143 


is  sometimes  the  most  laborious  undertaking  in  all  blood  ex- 
amination, but  it  is  also  one  of  the  most  important.  We  may 
search  two  or  three  hours  before  finding  one  nucleated  cor- 
puscle, but  on^  that  corpuscle  may  hang  the  character  of  our 
prognosis.  If  it  be  a  megaloblast  and  no  other  nucleated 
red  corpuscles  are  seen,  the  prognosis  is  bad,  and  it  is  impor- 
tant that  we  should  know  it.  This  is  particularly  true  when 
the  case  is  seen  during  a  remission,  for  under  these  conditions 
we  might  never  suspect  a  case  of  pernicious  anaemia  but  for  the 
presence  of  megaloblasts.  They  are  not  always  difficult  to  find; 
indeed,  in  one  of  my  cases  they  were  nearly  as  numerous  as  the 
white  cells,  but,  as  a  rule,  we  do  not  get  off  with  less  than  two 
hours'  work. 

The  following  table  (Table  III.)  shows  the  number  of  nucle- 
ated corpuscles  per  cubic  millimetre  in  thirty  of  the  cases  ex- 
amined by  the  writer. 

TABLE  III.— NUMBER  OF  NUCLEATED  RED  CELLS  PER  CUBIC  MILLIMETRE 
IN  THIRTY  CASES  OF  PERNICIOUS  ANAEMIA. 


Case  Number. 

Total  nucleated 
red  cells. 

Megaloblasts. 

Normoblasts. 

Microblasts. 

1    . 

7,100 

5,  300 

1,325 

475 

2  

6,468 

3,476 

924 

2,068 

3 

854 

574 

266 

14 

4 

277 

277 

0 

0 

5          

240 

160 

80 

6  

229 

123 

106 

7  

208 

130 

78 

8 

200 

134 

66 

9 

117 

103 

14 

10          

116 

80 

36 

11         

114 

95 

19 

12  

112 

96 

16 

13  

96 

96 

0 

14 

96 

84 

12 

15       

92 

59 

33 

16  

46 

26 

20 

17   '.  

45 

36 

9 

18 

39 

33 

6 

19 

35 

32 

3 

20 

28 

26 

2 

21  

28 

21 

7 

22  

28 

28 

0 

23  

18 

12 

6 

24 

14 

14 

o 

25  

11 

11 

0 

26  

11 

10 

1 

27  

11 

9 

2 

28 

9 

6 

3 

29 

8 

7 

1 

30....  

3 

2 

1 

144 


SPECIAL    PATHOLOGY    OF   THE   BLOOD. 


White  Corpuscles. 

Qualitative  CJianges. — Unless  the  cover-glasses    are   spread 
unusually  thick,  it  may  take  a  long  time  to  find  enough  leu- 

TABLE  IV.— PERCENTAGES  OF  LEUCOCYTES  IN  PERNICIOUS  ANAEMIA. 


LYMPHOCYTES,  LARGE  AND  SMALL. 

EOSINOPHILES. 

Number  of 
counts. 

No. 

Per  cent. 

No. 

Per  cent. 

1 

79. 

77. 
71. 
61.6 
58. 
57.6 
57.2 
57. 
56.9 
56. 
53.9 
53.8 
51.5 
49.5 
49.4 
47.9 
47.9 
47. 
46. 
45.9 
45.5 
44.7 
43.7 
42.2 
41. 
40.8 
40.5 
39. 
38. 
38. 
37.8 
36.1 
35.7 
35.6 
35.6 
34. 

1  

9. 
6.2 
6. 
4.7 
4.6 
4.5 
4.4 
4.3 
4. 
4. 
4. 
3.7 
3.5 
3.4 
3.4 
3.1 
3. 
2.8 
2.7 
2.6 
2.6 
2.6 
2.6 
2. 
2. 
2. 
1.6 
1.6 
1.5 
1.5 
1.5 
1.5 
1.4 
1.2 
1.2 
1.2 

1 
1 
1 
2 
2 
3 
1 
1 
1 
5 
1 
2 
1 
2 
1 
1 
3 
2 
2 
1 
3 
2 
1 
1 
1 
2 
1 
1 
5 
2 
1 
1 
1 
3 
1 
1 

2 

2 

3 

3  

4        -  . 

4  

5 

5  

6 

6  

7       

7  

8       

8  

9 

9 

10 

10       ... 

11 

11      

12 

12  

13 

13    

14 

14  

15 

15  

16 

16  

17       

17  

18 

18 

19 

19      

20 

20    

21 

21     

22 

22  

23         ... 

23  

24        

24  

25  

25  

26 

26 

27 

27 

28 

2$    

29 

29  

30    

30  

31 

31  

32  

32  

33  

33  
34 

34 

35     

35 

36.. 

36.. 

cocytes  for  an  accurate  differential  count,  so  great  is  the  leuco- 
penia  in  many  cases.  It  is  worth  while,  therefore,  to  spread 
some  cover-glasses  more  thickly  than  would  be  advisable  if  we 
had  only  the  red  cells  to  examine.  Such  preparations  should 
be  dried  at  once  by  artificial  heat. 

Lymphocytosis  is  the  chief  feature  (see  Table  IV.). 


THE   BLOOD    IN   PERNICIOUS   ANAEMIA. 


145 


TABLE  IV. —PERCENTAGE  OF  LEUCOCYTES  IN  PERNICIOUS  ANAEMIA 
(Continued) . 


LYMPHOCYTES,  LARGE  AND  SMALL. 

EOSINOPHILES. 

Number  of 
counts. 

No. 

Per  cent. 

No. 

Per  cent. 

37 

33.6 
33.1 
33. 
33. 

31.8 
29.4 
28.7 
28.4 
27.3 
27.2 
26.5 
24.2 
22. 
21.2 
19.8 
16. 

37 

1. 
1. 
1. 

.8 
.8 
.8 
.7 
.6 
.5 
? 
.3 
.2 
.0 
.0 
.0 
.0 

1 

2 
1 

1 
1 
1 
2 
1 
1 
1 

38         

38  .    . 

39  
40 

39  

40 

41 

41 

42 

42 

43   

43  

44     

44  

45  

45  

46 

46 

47 

47 

48 

48 

49     

49  . 

50  

50  .. 

51 

51 

52 

52 

In  52  cases  examined  by  myself  the  lymphocytes  (large 
and  small)  averaged  45.4  per  cent.  About  nine-tenths  of 
these  were  small  forms.  As  the  fatal  termination  approaches, 
the  percentage  of  lymphocytes  rises.  An  extreme  case  of  this 
change  has  already  been  recorded  on  page  90.  Two  other 
cases  showed  respectively  71  and  79  per  cent  of  lymphocytes 
a  few  days  before  death.  The  polymorphonuclear  cells 
suffer  proportionately  as  a  rule.  On  the  other  hand,  Ewing 
has  observed  a  marked  rise  in  the  percentage  of  the  poly- 
nuclear  cells  near  death,  although  autopsy  revealed  no  com- 
plication. 

Eosinophiles  are  occasionally  increased,  9  per  cent  being 
present  in  one  of  my  cases,  6.6  per  cent  in  another.  The  aver- 
age of  78  examinations  in  my  52  cases  is  2.7  per  cent. 

Small   percentages  of  myelocytes  are   the  rule.      They  are 
present  in  42  of  my  52  cases.     The  following  table  shows  the 
percentages : 
10 


146 


SPECIAL    PATHOLOGY    OF   THE    BLOOD. 


TABLE  V. 


No. 

Percentage 
of  myelocytes. 

No. 

Percentage 
of  myelocytes. 

No. 

Percentage 
of  myelocytes. 

1 

9.2 
8.8 
8. 
6.3 
6. 
4.6 
4. 
4. 
3.6 
3.4 
3. 
3. 
2.7 
2.5 
2.2 
2.2 
2.2 
2.0 

19 

1.8 
1.5 
1.5 
1.5 
1.4 
1.2 
1. 
1. 
1. 
1. 
1. 
.8 
.8 
.8 
.6 
.6 
.6 
.6 

37    . 

38 

0.6 
.6 
.5 
.4 
.3 
.2 
.0 
.0 
.0 
.0 
.0 
.0 
.0 
.0 
.0 
.0 

:  2  per  cont. 

2 

20 

3 

21 

39    ... 

4 

22 

40    .    . 

5 

23  

41  

6 

24  

42  
43  

7 

25  

8 

26 

44 

9  ... 

27  

45  .. 
46  

10           N 

28 

11 

29 

47  

12 

30  

48  

13 

31  

49  

14 

32 

50 

15 

33 

51  

16 

34 

52  

17 

35  

Average  - 

18 

36  

As  has  been  explained  above  (page  121),  the  inyelocyte  is 
found  in  a  great  variety  of  affections,  although  very  sparingly 
in  most,  but,  so  far  as  my  observations  go,  its  presence  is  more 
constant  and  the  percentages  run  higher  in  pernicious  anaemia 
than  in  any  other  disease  except  leukaemia.  I  am  speaking  now 
of  percentages.  With  a  leucopenia  such  as  is  usually  present 
in  pernicious  anaemia,  2  per  cent  of  myelocytes  means  absolutely 
a  very  small  number  per  cubic  millimetre. 

Taking  3,800  leucocytes  per  cubic  millimetre  as  the  average 
for  pernicious  anaemia  (see  above,  page  137)  2  per  cent  of  mye- 
locytes amounts  to  only  76  per  cubic  millimetre.  In  leukaemia 
the  absolute  number  of  myelocytes  is  seldom  under  150,000  per 
cubic  millimetre. 

The  more  important  characteristics  of  the  blood  of  pernicious 
anaemia  are  as  follows : 

1:  Red  cells  about  1,000,000  per  cubic  millimetre. 

2.  White  cells  much  diminished. 

3.  Haemoglobin  variable,  sometimes  increased  relatively  (= 
high-color  index). 

4.  Deformities  in  size  and  shape  of  red  cells  in  many  cases. 

5.  Increase  in  average  diameter  of  red  cells. 

6.  Polychromatophilic  red  cells. 


THE   BLOOD   IN   PERNICIOUS   ANAEMIA.  147 

7.  Megaloblasts  more  numerous  than  normoblasts. 

8.  Lymphocytosis. 

9.  Small  percentage  of  myelocytes. 

The  items  italicized  are  the  most  important  and  character- 
istic. 

Diagnostic  Value. 

1».  Pernicious  ancemia  and  chlorosis  may  be  indistinguishable 
without  the  examination  of  the  blood.  The  pallor  of  the  two 
diseases  is  not  always  different  either  in  degree  or  in  kind,  and 
the  symptoms  and  physical  signs  may  be  identical. 

The  differential  diagnosis  is  easily  made  by  the  blood. 
The  red  cells  rarely  reach  as  low  as  2,000,000  in  chlorosis  and 
the  number  and  degree  of  degenerative  changes  are  less  than  in 
pernicious  anaemia.  Megaloblasts  have  been  seen  in  chlorosis 
(Hammerschlag)  but  have  never  constituted  a  majority  of  the 
nucleated  red  cells  present.  In  the  great  majority  of  cases  the 
pallor  and  other  signs  and  symptoms  of  chlorosis  are  due  to 
lack  of  haemoglobin  per  corpuscle  (for  the  corpuscles  are  not 
only  pale  but  very  small-sized),  and  not  to  a  lack  of  corpuscles. 
The  high-color  index  and  large  size  of  the  scanty  cells  in  per- 
nicious anaemia  constrast  strongly  with  this. 

The  white  cells  are  about  the  same  in  both  diseases,  though 
usually  fewer  in  pernicious  anaemia.  Lymphocytosis  is  common 
to  both  diseases.  Myelocytes  are  occasionally  found  in  chlor- 
osis, but  much  less  commonly  than  in  pernicious  anaemia. 

2.  Pernicious  Ancemia  and  the  Anaemia  of  Malignant  Disease. 
— Not  long  ago  I  examined  the  blood  of  a  gentleman  who  had 
gradually  and  without  assignable  cause  acquired  a  "  lemon-yel- 
low" pallor,  without  loss  of  flesh,  vomiting,  pain,  or  any  localiz- 
ing sign  or  symptom.  The  diagnosis  of  pernicious  anaemia  had 
been  made.  To  my  great  surprise  I  found  over  4,000,000  red 
cells,  with  only  38  per  cent  of  haemoglobin,  and  18,780  white 
cells,  86  per  cent  of  which  were  polymorphonuclear  neutrophiles. 
One  normoblast  was  seen.  Fibrin  was  not  increased.  The 
anaemia  was  evidently  secondary,  and  the  autopsy  ten  months 
later  showed  cancer  of  the  stomach. 

Malignant  disease  may  bring  down  the  count  of  red  cells  to 
1,000,000  or  lower,  but  in  such  cases  leuocytosis  is  usually 
present.  As  will  be  seen  in  the  chapter  on  malignant  disease, 


148  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

leucocytosis  is  by  no  means  invariable  in  the  anaemia  of  can- 
cerous growth,  but  in  those  cases  which  cause  such  an  anaemia 
as  to  resemble  the  counts  of  pernicious  anaemia,  leucocytosis  is 
the  rule.  This  in  itself  is  usually  sufficient  to  exclude  uncom- 
plicated pernicious  anaemia.  Where  an  increase  in  the  whole 
number  of  leucocytes  is  not  present  in  malignant  disease, 
there  is  often  an  increased  percentage  of  polymorphonuclear 
cells,  contrasting  strongly  with  the  increased  percentage  of  lym- 
phocytes in  pernicious  anaemia.  Normoblasts  and  not  megalo- 
blasts  are  the  rule  in  malignant  disease.  If  megaloblasts  are 
present  they  are  in  the  minority,  while  in  pernicious  anaemia 
they  are  in  the  majority.  The  average  size  and  staining  power 
of  the  red  cells  is  increased  in  most  cases  of  pernicious  anaemia 
and  decreased  in  most  cases  of  malignant  disease. 

3.  Pernicious  Ancemia  and  other  Secondary  Ancemias. — Most 
secondary  anaemias  which  are  severe  enough  to  reduce  the  count 
of  red  cells  below  2,000,000  follow  the  type  of  malignant  dis- 
ease and  show  leucocytosis.     The  great  pallor  and  dyspnoea 
seen  in  connection  with  some  cases  of  tuberculosis  and  nephritis 
rarely  mean  a  low  count  of  red  cells,  but  simply  a  loss  of 
haemoglobin.     I  remember  two  cases  in  adjacent  beds  at  the 
Massachusetts  General  Hospital,  both  with  extreme  yellow  pal- 
lor without  emaciation;  one  had  1,020,000  and  the  other  4,100,- 
000  red  cells,  the  haemoglobin  in  each  being  about  thirty  per 
cent.     The  first  was  pernicious  anaemia,  the  second  nephritis. 

Purpura,  typhoid,  lead  poisoning,  chronic  malaria,  and  other 
diseases  may  reduce  the  red  cells  to  a  point  as  low  as  that  seen 
in  early  stages  of  pernicious  anaemia  and  may  not  be  accompa- 
nied by  leucocytosis;  but  the  absence  of  changes  most  charac- 
teristic of  the  latter  disease  (a  majority  of  megaloblasts,  in- 
creased diameter  and  color  index  in  the  red  cells)  serves  to  make 
the  diagnosis  clear.1 

4.  Pernicious  Ancemia  and  Leukcemia. — Occasionally  in  in- 
fants these  two  diseases  seem  to  approach  very  near  each  other 
and  are  difficult  to  distinguish.     In  infancy,  as  is  well  known, 
any  anaemia  (primary  or  secondary)  is  apt  to  be  accompanied  by 

1  Another  point  of  difference  emphasized  by  Grawitz  is  that  the  plasma 
of  pernicious  anaemia  has  a  relatively  larger  amount  of  solids  than  that  of 
anaemia  secondary  to  the  above  diseases.  This  is  hardly  a  clinically  ap- 
plicable test,  but  is  said  to  be  a  valuable  one. 


THE   BLOOD    IN   PERNICIOUS   ANEMIA.  149 

leucocytosis  and  an  enlarged  spleen.  Further  leukaemia,  which 
in  adults  usually  causes  a  relatively  slight  anaemia,  affects  the 
red  cells  much  more  strongly  in  infancy,  and  may  reduce  them 
to  a  number  decidedly  suggestive  of  pernicious  anaemia.  There- 
fore in  both  diseases  we  may  have  enlarged  spleen,  great  anae- 
mia, and  leucocytosis. 

The  one  characteristic  point  of  leukaemic  blood — the  abun- 
dance of  myelocytes — usually  enables  us  to  distinguish  the  two 
diseases,  for  although  present  in  both  diseases  the  myelocyte 
is  much  more  plentiful  in  leukaemia.  Unfortunately  we  have 
no  way  of  fixing  just  how  numerous  myelocytes  must  be  in 
order  to  constitute  leukaemia.  It  is  only  in  infancy  and  very 
rarely  then  that  this  difficulty  arises,  but  at  that  period  I  am 
inclined  to  believe  that  we  sometimes  see  conditions  intermedi- 
ate between  the  two  diseases,  indicating  the  ultimate  identity  of 
the  two.  Their  numerous  clinical  resemblances  cannot  here  be 
discussed.  (For  further  comment  on  this  point  see  page  395.) 

PROGNOSTIC  VALUE  or  THE  BLOOD  IN  PERNICIOUS  ANAEMIA. 

The  prognosis  is  always  very  bad,  but  the  following  scheme 
indicates  the  presence  of  a  severe  or  of  a  mild  type: 

1.  Severe  (rapidly  fatal).  2.  Less  Severe  (slower  course), 

(a)  Extreme    progressive    an-  (a)  Remissions. 

asmia.  (b)  Normal  or  low-color  index, 

(ft)  High-color  index.  (c)  Normal-sized  or  small  cells. 

(c)  Increase  in  size  of  red  cells.  (d)  No  degenerative  change. 

(d)  Degenerative  changes.  (e)  Numerous  normoblasts. 

(e)  Numerous  megaloblasts.  (/)  Few  megaloblasts. 

(/)  Few  or  no  normoblasts.  (g)  Normal  percentage  of  poly- 

(g)  Lymphocytosis.  morphonuclear  cells. 

It  has  been  thought  by  some  observers  that  the  absence  or 
great  scantiness  of  nucleated  corpuscles  indicated  lack  of  any 
effort  at  regeneration  on  the  part  of  the  blood-making  functions 
and  hence  a  peculiarly  malignant  type  of  the  disease.  I  have 
never  seen  cases  in  which  no  nucleated  corpuscles  were  present, 
but  their  scantiness  has  seemed  to  me  as  a  rule  to  be  associated 
with  a  more  slowly  fatal  type  of  the  disease. 

No  significance  has  seemed  to  me  to  attach  to  the  presence 
of  larger  or  smaller  percentages  of  eosinophiles. 


150 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


Pernicious 
anaemia. 

Chlorosis. 

Secondary 
anaemia. 

Leukaemia  in 
infancy. 

Red  cells  
White  cells.... 

Haemoglobin  .  . 
Megaloblasts  .  . 

Normoblasts  .  . 

Size  of  red  cells 
Lymphocytes.. 

Polymorphonu- 
clear  cells. 
Myelocytes.... 

About  1,000,000.... 
Usually  decreased. 

Often    relatively 
high. 
Constitute  the  ma- 
jority of  the  nu- 
cleated red  cells. 
L  e  s  s  •  numerous 
than  the  megalo- 
blasts. 

Increased  

Rarely    under    2,- 
000,000. 
Usually  normal.... 

Always    relatively 
low. 
Rare  

May  be  1,000,000 
or  less. 
Usually    in- 
creased. 

Relatively  low... 

Rare;  never  more 
numerous  than 
normoblasts. 

May   be    under 
2,000,000. 
Usually  more  in- 
creased than  in 
any    other   dis- 
ease. 
Relatively  low. 

Common  . 
Common. 

Various;    not   in- 
creased. 
Usually  increased. 

Usually    d  i  m  i  n  - 
ished. 
Usually  more 
numerous    than 
in  other  diseases. 

Occasional;  always 
more    numerous 
than     megalo- 
blasts. 
Diminished  

Various;   not  in- 
creased. 
Usually  d  i  m  i  n  - 
ished. 
Usually    in- 
creased. 
Rare  

Decreased  .  . 

Decreased 

Common  

Bare  

To  illustrate  the  different  size  of  the  cells  in  chlorosis  and 
pernicious  anaemia  I  have  had  photographs  taken  of  the  blood 
of  a  case  of  two  of  these  diseases  and  of  normal  blood,  all  on  pre- 
cisely the  same  scale.  See  Figs.  31,  32,  33. 


FIG.  31.— Normal  Blood.    Magnified  350  diameters, 


THE   BLOOD   IN   PERNICIOUS   ANAEMIA. 


151 


Fis.  32.— Pernicious  Anaemia.     Magnified  350  diameters.     Note  the  relatively  large  size  and 
well-stained  centres  of  the  cells. 


FIG.  33.— Chlorosis.     Magnified  350  diameters.     Note  small  size  and  pale  centres. 


152  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

2.  THE  BLOOD  IN   CHLOROSIS. 

This  has  been  already  described  for  the  most  part  under  the 
heading  of  Secondary  Anaemia.  In  many  cases  the  two  are  in- 
distinguishable by  the  blood  examination  alone,  the  changes 
consisting  simply  in  the  presence  of  light,  small-sized,  pale, 
more  or  less  deformed  red  cells  ^  whose  number  may  or  may  not 
be  decreased,  according  to  the  severity  of  the  case.  Leucocy- 
tosis  is  rarely  if  ever  present  in  uncomplicated  chlorosis,  but  is 
often  absent  in  secondary  anaemia.  Normoblasts  may  be  pres- 
ent in  both.  The  chief  points  of  distinction  are : 

(a)  The  red  cells  are  more  apt  to  be  uniformly  undersized 
and  under-colored  in  chlorosis,  while  in  secondary  anaemia  we 
more  often  find  normal  cells  among  the  diseased  ones. 

(b)  The  color  index  may  be  lower  in  chlorosis  than  is  com- 
mon in  secondary  anaemia,  and  this  lowering  is  more  constant  in 
chlorosis. 

(c)  Lymphocytosis,  which  is  very  common  in  chlorosis,  is  not 
so  common  in  secondary  anaemia. 

(d)  Nucleated  corpuscles  are  less  common  in  chlorosis  than 
in  anaemia  secondary  to  malignant  disease. 

(e)  Coagulation  is  rapid,  in  contrast  with  the  very  slow  clot- 
ting of  pernicious  anaemia  and  of  many  secondary  anaemias. 
Yet  fibrin  is  not  increased. 

The  Mood  in  Gross. 

The  pallor  of  the  drop  is  sometimes  excessive,  fully  as  great 
as  in  pernicious  anaemia,  and  the  liquid  is  very  fluid  and  thin. 
Yet  it  coagulates  very  rapidly  and  our  technique  must  be 
prompt. 

BED  CELLS  AND  HAEMOGLOBIN. 
Quantitative  Changes. 

Hay  em  has  recorded  cases  whose  count  was  as  low  as  1,662,- 
000  and  even  937,360  per  cubic  millimetre.  Such  figures  are 
certainly  rare  in  this  country,  and  the  striking  fact  is  usually 
the  slight  numerical  loss  of  red  cells,  considering  the  extreme 
pallor  of  the  patients. 


THE   BLOOD   IN    CHLOROSIS.  153 

The  lowest  count  in  the  Massachusetts  Hospital  series 
was  1,932,000,  and  in  W.  S.  Thayer's  63  cases  1,953,000. 
The  accompanying  tables,  from  the  Massachusetts  Hospital 
records,  show  the  range  of  red  cells  and  haemoglobin  in  109 
cases  as  counted  when  the  patients  first  came  under  obser- 
vation. The  highest  counts  (7,100,000  and  5,884,000)  are  un- 
doubtedly due  to  some  temporary  stasis  or  concentration  of  the 
blood. 

The  average  of  the  109  cases,  4,112,000  red  cells  per  cubic 
millimetre,  is  remarkable  in  so  nearly  coinciding  with  Thayer's ' 
series  above  referred  to,  the  average  of  which  is  4,096,544. 

The  average  haemoglobin  percentage  of  this  series,  41.2  per 
cent,  is  also  very  close  to  Thayer's  (42.3  per  cent).  This  gives 
us  on  the  average  a  reduction  of  the  corpuscle  substance  to  one- 
half  the  normal,  or  to  the  equivalent  of  2,250,000  healthy  red 
cells;  61  of  the  109  cases  have  4,000,000  or  more  red  cells. 
These  figures  do  not  agree  with  those  collected  by  v.  Limbeck, 
in  which  only  99  out  of  247  are  over  4,000,000.  But  this  prob- 
ably means  simply  that  in  this  country  the  patients  seek  medical 
advice  before  their  disease  has  advanced  very  far,  while  in  Ger- 
many they  wait  longer  before  resorting  to  a  hospital.  For,  as 
above  explained,  in  all  anaemias  the  individual  corpuscles  suffer 
in  quality  first  and  only  after  some  time  begin  to  decline  in 
number.  This  is  especially  the  case  in  chlorosis,  although  by 
no  means  peculiar  to  that  disease. 

The  color  index  is  invariably  low,  as  seen  in  the  table,  al« 
though  it  is  rare  to  see  it  fall  below  .30.  In  only  four  cases  of 
the  present  series  did  it  go  below  that  figure,  the  average  being 
about  .50. 

v.  Noorden 2  found  that  the  color  index  was  especially  apt  to 
be  low  in  first  attacks  and  less  often  in  the  recurrent  or  habitual 
cases,  but  Eomberg  3  in  a  study  of  one  hundred  and  seventeen 
cases  has  not  found  this  true,  and  I  agree  with  Eomberg.  One 
of  the  lowest  color  indexes  in  my  series  was  in  a  woman  over 
fifty  who  had  a  truly  habitual  chlorosis. 

1  See  Osier's  article  on  Chlorosis  in  the  "American  Text-Book  of  Medi- 
cine," vol.  ii.,  1894. 

2  Chlorosis:  Wien,  1897  (Holder). 
*Berl.  klin.  Woch.,  June  28th,  1897. 


154  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 


TABLE  VI. — CHLOROSIS. 

Red  Cells.  Cases. 

Between  7, 000, 000  and  8, 000, 000 . 


6,000,000    " 

7,  000,  000 

1 

5,000,000    " 

6,000,000  

17 

4.000,000    " 

5,000,000  

42 

3,000,000    " 

4,  000,  000  

33 

2,000,000    " 

3,000,000  

14 

1,000,000    " 

2,000,000  

i 

Average  of  these  109  cases  =  4,112,000 


White  Cells. 
Between  15,000  and  14,000 

Cases. 

2 

•\ 
Between 

kVhite  Cells. 
7,  000  and  6,  000  ... 

Cast 
19 

"        14,000    "     13,000 

1 

6,000    "    5,000... 

11 

13,000    "     12,000 

3 

u 

5,000    "    4,000... 

9 

12,000    "     11,000 

5 

tt 

4  000    ''    3  000 

7 

11,000    "    10,000.. 
10,000    "      9,000.. 
9,000    "      8,000.. 
"          8,000    "      7,000.. 

...     9 
...     6 

...     7 
...  23 

it 

3,000    "    2,000.. 
2,000    "    1,000... 

1 
1 

104 

Average,  7,400. 

PER  CENT  OF   HAEMOGLOBIN  IN   CHLOROSIS. 

Between  10  aud  19  =   7  cases. 


20  " 

29  =  13  " 

30  " 

39  =  28  " 

40  " 

49  =  25  " 

50  " 

59  =  24  " 

60  " 

69=  7  " 

70  " 

79=  1  " 

105 

Average, 

41  per  cent. 

The  striking  contrast  is  with  pernicious  anaemia,  rather  than 
with  secondary  anaemia.  In  the  former  the  color  index,  as 
above  mentioned,  averaged  1.04  in  68  cases.  In  secondary 
anaemia  it  is  almost  always  below  1,  but  does  not  average  so  low 
as  in  chlorosis,  although  in  individual  cases  it  may  be  very  low. 
For  example,  Osterspey  quotes  a  case  of  gastric  cancer  with 
a  blood  count  of  4,230,000  red  cells,  and  only  22  per  cent  of 
haemoglobin,  a  color  index  of  .26. 


THE  BLOOD  IN  CHLOROSIS.  155 

BED  CELLS  (CONTINUED). 
Qualitative  Changes. 

(a)  The  stained  specimen  shows  a  greater  or  less  degree  of 
pallor  of  the  corpuscle  centres  corresponding  so  accurately  to  the 
diminution  in  haemoglobin  that  a  practised  observer  can  tell  ap- 
proximately how  low  it  is  simply  from  the  stained  specimen. 
The  pallor,  however,  is  to  be  taken  in  connection  with  the  size  of 
the  cells,  for  the  diminution  in  haemoglobin  is  not  due  simply  to 
a  bleaching  out  of  the  cells,  but  to  their  loss  of  size.     Hence, 

(b)  The  diminution  in  the  average  diameter  of  the  cells  is  a 
very  important  feature.     Both  in  this  respect  and  as  regards  the 
bleaching  of  individual  cells,   many  cases  contrast  with  most 
secondary  anaemias,  in  that  a  large  proportion  of  the  cells  are 
affected  alike,  i.e,  are  small  and  pale,  while  in  secondary  anae- 
mia there  are  apt  to  be  well-stained  and  good-sized  or  over- 
sized cells  in  every  field.     These  last  occur  also  in  chlorosis,  but 
less  frequently  as  a  rule.     Hence  the  usually  lower  color  index 
of  chlorosis.     In  certain  cases  this  distinction  does  not  hold  and 
the  two  conditions  are  identical  in  so  far  as  the  size  and  color  of 
the  red  cells  are  concerned.     It  is  to  the  white  cells  that  we  must 
look  for  help  in  differential  diagnosis. 

(c)  Deformities  in  size  and  slmpe  are  very  common  in  all  ad- 
vanced cases,  but  often  absent  in  mild  or  moderate  ones.     They 
present  no  special  peculiarities  except  that  macrocytes  are  rela- 
tively rare  and  microcytes  relatively  common.     In  the  severest 
cases,  however,  the  macrocytes  begin  to  get  more  numerous  and 
we  approach  the  picture  of  pernicious  anaamia. 

(d)  Degenerative  changes  (Maragliano,  see  page  88)  are  not 
common  but  are  occasionally  present  in  severe  cases. 

(e)  Nucleated  red  corpuscles  are  very  scanty  even  in  advanced 
cases.     Hay  em  never  saw  any,  but  most  observers  find  them  in 
small  numbers  after  long  search.     They  are  almost  always  of 
the  normoblast  type,  but  megaloblasts  have  also  been  found. 

The  scantiness  of  nucleated  red  cells  is  a  point  of  contrast  with 
the  anaemia  secondary  to  malignant  disease,  in  which  even  in 
mildly  anaemic  states  we  readily  find  nucleated  corpuscles,  while 
in  chlorosis,  even  in  severe  cases,  a  long  search  may  show  very 
few  or  even  none  at  all. 


156  SPECIAL    PATHOLOGY    OF   THE    BLOOD. 

Specific  Gravity. 

Chlorosis  is  usually  agreed  to  be  one  of  the  diseases  in  which 
specific  gravity  and  haemoglobin  run  parallel,  and  as  the  inac- 
curacies and  inconveniences  of  the  v.  Fleischl  instrument  are 
so  great,  it  seems  to  the  writer  better  to  follow  the  specific 
gravity  rather  than  the  haemoglobin.  The  tables  on  page  42 
(Part  I. )  show  how  the  inference  from  density  to  coloring  matter 
can  be  made.  A  specific  gravity  of  1030  is  not  very  rare. 

WHITE  CELLS. 
A.   Quantitative  Changes. 

Leucocy  tosis  is  absent  in  uncomplicated  cases.  In  the  series 
in  Table  YI.  the  occasional  leucocy  tosis  may  be  due  to  digestive 
or  to  a  variety  of  other  influences  (uterine  troubles,  etc.),  which 
could  not  be  excluded. 

The  average  in  Thayer's  63  cases  was  8,467;  in  the  present 
series  (see  Table  YI.)  it  is  7,485. 

As  in  pernicious  anaemia,  the  worst  cases  are  apt  to  have 
leucopenia,  and  as  improvement  progresses  the  white  rise  even 
faster  than  the  red  corpuscles. 

Thus  in  Romberg's  careful  study  of  117  cases,  24  cases 
whose  haemoglobin  was  under  40  per  cent  had  an  average  of 
6,350  leucocytes  per  cubic  millimetre,  while  52  cases  whose 
haemoglobin  averaged  60  per  cent  had  an  average  of  9,250 
leucocytes.  He  found  the  average  in  healthy  girls  of  the  same 
age  9,068  white  cells  per  cubic  millimetre. 

The  absence  of  leucocytosis  is  the  most  important  point  in 
distinguishing  chlorosis  from  secondary  anaemia  due  to  cancer, 
suppuration,  etc. 

B.   Qualitative  Changes. 

Lymphocyte-sis  is  usually  present,  as  in  pernicious  anaemia, 
wherever  the  disease  is  well  marked,  and  sometimes  even  in  mild 
cases.  Thus  Eieder  found  in  12  cases  an  average  of  33  per  cent 
of  lymphocytes,  the  highest  percentages  being  53.7,  43.5,  and 
41.7.  Either  the  small  or  the  large  lymphocytes  may  pre- 
dominate. In  my  own  experience  it  has  usually  been  the  small 
forms. 


THE   BLOOD    IN   CHLOROSIS.  157 

The  neutrophiles  suffer  proportionally,  their  low  percentage 
contrasting  often  with  that  of  secondary  anaemia  associated  with 
leucocytosis.  Eosinophiles  are  occasionally  increased.  In 
Eieder's  12  cases  the  average  percentage  was  3.5,  the  highest 
percentages  being  9.6  and  7  per  cent. 

Myelocytes  are  rare  but  have  occasionally  been  observed  in 
small  numbers. 

Regeneration  of  the  Blood. 

As  the  patients  begin  to  mend  under  the  influence  of  treat- 
ment, the  blood  changes  are  just  the  reverse  of  those  seen  dur- 
ing the  development  of  the  disease.  First  the  corpuscles  gain 
in  numbers,  the  haemoglobin  still  remaining  low;  later  and 
much  more  slowly  the  coloring  matter,  size,  and  weight  of  the 
cells  are  renewed.  It  seems  as  if  the  new-formed  cells  were  of 
light  weight  and  had  to  be  replaced  gradually  by  cells  of  normal 
stature.  The  nucleated  corpuscles  and  deformities  disappear 
and  the  leucocytes  shoot  up  often  a  little  above  the  normal. 

Slood  Plates. 
"Usually  considerably  increased. 

Chlorosis  without  Known  Blood  Changes. 

Eomberg  quotes  the  following  facts :  Three  girls,  nineteen, 
twenty,  and  twenty-five  years  of  age,  came  to  him  with  typical 
symptoms  of  chlorosis.  Their  blood  counts  showed : 

I.  Eed  cells,  5,246,000;  Hb.,  80  per  cent. 

II.  "       "     5,376,000;    "       83 

III.  "       "     4,408,000;    "       87 

All  improved  markedly  under  iron  treatment. 

I  mention  this  because  I  have  seen  several  similar  cases  and 
have  heard  of  others  from  colleagues. 

Summary. 

1.  Blood  as  a  whole :    Very  pale  in  marked  cases,  very  fluid, 
but  coagulates  rapidly.     Fibrin  not  increased.     Specific  gravity 
usually  low,  running  parallel  with  the  haemoglobin. 

2.  Ked  cells :   Average  4,000,000  when  patient  is  first  seen, 


158  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

very  rarely  go  below  1,000,000.  The  majority  of  them  are 
small-sized,  pale,  often  deformed.  Nucleated  corpuscles  are  rare 
(normoblasts  as  a  rule). 

3.  White  cells,  not  increased. 
Lymphocytosis,  occasionally  eosinophilia. 

4.  Blood  plates  increased. 

Diagnostic  Value. 

1.  The  points  of  difference  from  pernicious  anaemia  have 
been  discussed. 

2.  It  is  important  to  distinguish  it  from  simple  debility, 
and  from  cases  whose  skin  only  is  anaemic;  in  both  of  these 
conditions  the  blood  is  normal. 

3.  From  secondary  anaemia  it  may  be  indistinguishable  in 
case  the  latter  be  without  leucocytosis.     Where  leucocytosis  is 
constantly  present  and  the  percentage  of  polymorphonuclear 
leucocytes  is  increased,  chlorosis   (uncomplicated)  can  be  ex- 
cluded.    Of  course  many  of  the  complications  which  may  occur 
in  chlorosis  are  accompanied  by  leucocytosis. 

Other  Forms  of  Ancemia. 

1.  Cases  of  acute  fatal  anaemia  following  purpura  or  severe 
hemorrhage  of  any  kind  are  sometimes  classed  as  pernicious 
anaemia.  The  blood  certainly  differs  in  many  respects  from 
that  of  ordinary  pernicious  anaemia.  Ehrlich  describes  such  a 
case  following  metrorrhagia  in  which  the  red  cells  were  re- 
duced to  213,360  per  cubic  millimetre  without  much  deformity 
of  individual  cells  and  with  a  decided  decrease  in  the  average 
diameter.  Poly  chroma  tophilic  forms  numerous.  No  nucleated 
corpuscles  whatever  could  be  found  even  after  many  hours' 
search.  The  leucocytes  were  decreased  to  about  200  (!)  per 
cubic  millimetre.  Eighty  per  cent  of  them  were  small  lympho- 
cytes, six  per  cent  large  lymphocytes,  and  only  fourteen  per 
cent  polymorphonuclear.  Eosinophiles  and  myelocytes  ab- 
sent. Autopsy  showed  no  red  marrow  in  the  long  bones  except 
at  the  epiphysis,  and  an  entire  lack  of  effort  on  regeneration. 

W.  S.  Thayer  has  observed  two  similar  cases,  and  Bignami 
and  Dionisi  have  seen  cases  of  the  same  kind  following  the 


THE   BLOOD   IN   CHLOROSIS. 


159 


prolonged  deglobularizing  action  of  the  malarial  organisms.     I 
have  never  seen  just  this  type  of  anaemia. 

2.  Some  cases  of  severe  chronic  chlorosis  seem  to  belong  in  a 
separate  category.  Like  the  variety  last  described  the  blood  is 
here  of  the  microcyte  type,  the  diameter  of  the  corpuscles  being 
greatly  reduced.  I  have  observed  one  case  somewhat  similar 
in  a  male  of  fifty-two,  a  carpenter  whom  I  had  noticed  for 
several  years  at  his  work,  the  palest  man  I  ever  saw  out  of  bed. 
About  two  years  ago  I  had  an  opportunity  to  examine  his  blood, 
he  feeling  well,  at  work,  and  objecting  to  the  bother  of  the 


FIG.  34.— Chronic  Secondary  Anaemia  due  to  Bleeding  Piles.    Magnified  350  diameters. 
Note  the  similarity  to  chlorotic  blood  (Fig.  33,  page  151). 

examination.  His  blood  showed:  Eed  cells,  2,530,000;  white 
cells,  2,000 ;  haemoglobin,  32  per  cent. 

The  red  corpuscles  were  not  at  all  deformed  but  were  very 
small  (see  Fig.  34)  and  very  pale  in  the  centre.  While  counting 
1,200  white  cells  17  normoblasts  were  seen;  no  megaloblasts. 
The  leucocytes  showed :  Polymorphonuclear  neutrophiles,  54.5 ; 
small  lymphocytes,  35 ;  large  lymphocytes,  9.4;  eosinophiles,  1.1. 

The  man  is  still  well  and  hearty,  complains  of  nothing,  but 
is  as  pale  as  ever.  A  few  days  ago  he  disclosed  to  me  that  he 
had  had  bleeding  piles  for  ten  years.  He  had  been  hitherto 
concealing  this  fact. 


CHAPTEE  II. 

I.  LEUKAEMIA. 

THE  distinction  between  leukaemia  and  leucocytosis  has  been 
sufficiently  dwelt  on  above. 

The  blood  of  the  vast  majority  of  oases  of  leukaemia  falls 
clearly  under  one  or  the  other  of  two  distinct  types,  myelocytwm.ia 
on  the  one  hand,  lymphcemia  on  the  other.  Myelocytaemia  is 
only  found  in  cases  with  great  hypertrophy  of  the  spleen,  marked 
marrow  changes,  and  little  or  no  enlargement  of  the  other  lym- 
phatic tissue.  Such  cases  are  usually  chronic  (two  to  five  years). 
Lymphaemia,  on  the  other  hand,  may  be  associated  either  with 
acute  or  chronic  forms  of  the  disease,  and  while  in  all  cases  of 
lymphaemia  we  have  some  set  of  lymphatic  glands  enlarged 
there  may  be  no  externally  visible  glands  enlarged,  and  the 
spleen  may  be  as  big  as  in  cases  associated  with  myelocytaemia. 
The  diagnosis  of  leukaemia  can  easily  be  made  by  the  blood 
alone,  but  we  cannot  say  from  the  blood  whether  or  not  the 
spleen  or  visible  lymph  glands  are  the  organs  chiefly  involved. 
In  acute  cases  the  lymph  glands  of  the  alimentary  tract  (cer- 
vical, faucial,  gastro-enteric,  mesenteric)  may  be  the  only  set 
involved. 

All  of  the  thirty-one  cases  associated  with  myelocytaemia 
which  have  come  under  my  observation  have  run  a  chronic 
course,  while  of  the  cases  showing  lymphaemia  five  were 
chronic,  three  acute,  and  two  subacute.  All  showing  myelo- 
cytaemia  had  very  large  spleens  without  enlargement  of  visible 
lymph  glands,  but  two  of  the  lymphaemias  had  spleens  almost 
filling  the  abdomen. 

The  disease  leukaemia,  then,  is  associated  with  three  types 
of  blood. 

1.  Chronic  myelocytaemia. 

2.  Chronic  lymphaemia. 

3.  Acute  lymphaemia. 


LEUKEMIA. 


161 


1.  MYELOCYT^EMIA. 
(Splenic-myelogenous  leulccemia. ) 

The  drop  as  it  emerges  from  the  puncture  looks  somewhat 
opaque  in  color,  but  is  neither  whitish  nor  chocolate  colored. 
It  flows  very  sluggishly,  however,  and  is  difficult  to  spread 
between  cover-glasses  owing  to  the  masses  of  white  cells  con- 
tained in  it.  Coagulation  is  slow. 

KED  CELLS. 

In  early  stages  of  the  disease  there  is  no  anaemia.  Later  the 
diminution  in  red  cells  is  moderate,  averaging  about  3,120,000 
in  the  thirty -nine  cases  of  Table  VII.,  A.  The  patients  are 
often  not  pale  and  may  feel  perfectly  well.  The  haemoglobin 
is  usually  diminished,  the  color  index  being  about  0.6  in  my 
cases.  It  is  difficult  to  read  the  v.  Fleischl  instrument  in  leu- 
kaemia, as  the  presence  of  so  many  leucocytes  gives  a  muddy 
tint  to  the  liquid,  not  easy  to  compare  with  the  red  of  the 
glass. 

TABLE  VII. — LEUKAEMIA. 


A 

L 

B 

No. 

Red  cells. 

No. 

White  cells. 

1.. 
2  .. 

Highest  .  .  . 

5,000,000 
4  877  000 

1  

2 

Highest  .  . 

1,072,222 
980  000 

3  

4  800  000 

3 

820  000 

4.... 

4,  592,  000 

'4  ... 

800  000 

5  

4,  288,  000 

5 

756  000 

6.... 

4,016,000 

6 

748  000 

7.... 

3,760,000 

7 

716  000 

8 

3  635  570 

8 

656  000 

9.... 

3  605  000 

9 

626  600 

10.... 

3  400  000 

10 

570  000 

11.... 

3,292,000 

11.... 

500  000 

12  ... 

3  200  000 

12 

492  000 

13.... 

3,080,000 

13 

454  000 

14.... 

3  078  000 

14 

448  000 

15.... 

3  010  000 

15 

430  000 

16.... 

2  996  000 

16 

428  000 

17.... 

2  960  000 

17 

405  000 

18.... 

2,  938,  000 

18 

400  000 

19.... 

2  921  600 

19 

394  000 

20.. 

2  868  000 

20 

386  000 

21.... 

2,792,000 

21.. 

340,000 

11 


162 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


TABLE  VII.  —LEUKAEMIA  (Continued). 


A 

B 

No. 

Red  cells. 

No. 

White  cells. 

22 

2,  738,  000 
2,715,000 
2,576,000 
2,  520,  000 
2,  322,  222 
2,320,000 
2,256,000 
2,140,000 
2,112,000 
2,060,000 
2,016,000 
2,010,000 
1,866,664 
1,420,000 
1,386,000 
1,358,000 
1,200,000 
408,  000 

3  =  3,131,000  + 

22 

320,000 
290,000 
•     260,  000 
220,  500 
213,000 
188,000 
183,  000 
175,  800 
170,000 
139,  600 
138,000 
134,400 
132,000 
111,000 
98,  000 

age  =  428,  000 

23.    .. 
24.... 
25  

23  

24.... 

25.... 
26 

26 

27 

27.... 
28 



28.... 

29  ... 

29   . 

30.... 

30  .. 

31 

31 

32 

32 

33 

33.... 
34.... 
35 

34.... 

35.... 

36 

36.  ... 

Lowest  .  .  . 
Aver 

37.... 

38 



39.  ... 

Lowest  .... 
Averag 

Qualitative  Changes. 

The  striking  point  is  the  presence  of  very  numerous  nucleated 
red  cells  even  in  the  absence  of  any  sign  of  ancemia.  With  over 
4,000,000  well-formed  and  well-colored  red  cells,  we  may  have 
hundreds  of  nucleated  ones  in  every  cover-glass.  They  are  as 
numerous  in  this  form  of  leukaemia  as  in  the  worst  forms  of 
pernicious  anaemia,  even  tho.ugh  the  patient  may  be  feeling 
nearly  well. 

Both  normoblasts  and  megaloblasts  may  be  seen,  but  in 
most  cases  the  latter  are  in  the  minority.  Many  of  the  normo- 
blasts show  fragmentation  in  their  nuclei,  and  occasionally  true 
karyokinetic  figures  are  to  be  seen.  In  the  anaemic  cases  we 
find  all  the  other  changes  in  the  red  cells  characteristic  of 
anaemia,  but  the  nucleated  cells  are  always  more  prominent 
than  in  any  other  form  of  anaemia  of  a  like  severity.  This 
shows  that  nucleated  corpuscles  are  not  to  be  thought  of  as 
evidence  (like  deformities  in  shape)  of  regenerative  or  degener- 
ative conditions  only.  A  special  connection  to  the  bone  marrow 
is  very  clearly  indicated,  all  the  more  so  as  in  the  lymphatic 


PLATE  II 

FIG.  1.— Both  this  and  Fig.  2  are  intended  to  be  fac-similes  of  actual 
microscopic  fields. 

(a)  Note  the  cell  between  those  labelled  8  and  9 — apparently  a  "  mast 
cell."  Such  cells  are  often  seen  in  this  form  of  leukaemia.  With  Ehrlich's 
stain  they  present  this  appearance.  Basic  stains  bring  out  coarse  blue 
granules  on  the  periphery  of  the  protoplasm. 

(5)  Note  also  the  cell  at  the  extreme  upper  right-hand  corner  of  Fig.  1, 
which  it  is  almost  impossible  to  classify  either  as  a  myelocyte  or  as  a 
polymorphonuclear  neutrophile,  since  it  appears  to  be  intermediate  be- 
tween the  two  varieties. 

(c)  Both  the  nucleated  corpuscles  are  normoblast  *,  9  has  polychromato- 
philic  protoplasm.  The  red  cells  show  scarcely  any  deformities  and  very 
slight  deficiency  in  coloring  matter. 

FIQi  2.  —  (a)  Note  the  deformities  in  size  and  shape  of  red  corpuscles, 
owing  to  the  anaemia  present. 

(6)  No  lymphocytes  are  figured,  as  they  made  up  only  two  per  cent  of 
the  white  cells  in  this  case.     Eosinophiles  were  absent. 

(c)  Note  that  the  contrast  between  this  figure  (leucocytosis)  and  the  one 
above  it  (leukaemia)  is  not  in  the  abundance  of  white  cells  but  in  the  kind 
of  white  cell  predominating  among  those  present. 


Examination  of  the  Blood. 


PLATE  II. 


Figure  I  =  Splenic-myelogenous  Leucaemia 
Figure  II  =  Leucocytosis  (cancer  of  kidney) 
Cells  stained  yellow  =  Red  corpuscles 

1.  2.  3.  4  a.  5  =  Polymorphonuclear  neutrophiles 

6  =  Lymphocyte 

7  a.  8.  =  Eosinophiles 

9  a,  10  =  Nucleated  red  corpuscles 

All  others  =  Myelocytes 

~,* 


Figure  I 
Leucaemia. 


Cells  stained  yellow  =  Bed  corpuscles 
All  others  = 
Polymorpho- 
nuclear- 
neutrophiles 


Figure  II 
Leucocytosis. 


Scale  of 


R.  C.    Cabot  fee. 


Lith.  Anat.  T.  E.  A.  Kunk«,  Leipzig. 


LEUKAEMIA.  163 

form  of  the  disease  in  which  the  bone  marrow  is  usually  much 
less  affected,  nucleated  corpuscles  are  much  less  numerous,  ap- 
pearing in  relatively  small  numbers  in  the  very  acute  anaemic 
cases  and  not  at  all  in  those  who  are  not  anaemic. 

Other  qualitative  changes  are  not  marked  and  correspond  to 
the  degree  of  anaemia  present ;  often  there  are  none  at  all. 

As  the  count  of  the  white  cells  rises,  that  of  the  red  may  fall, 
and  vice  versa ;  or  the  red  cells  may  remain  at  a  comparatively 
high  figure  despite  the  progress  of  the  white. 

WHITE  CELLS. 
Quantitative  Changes. 

The  average  number  per  cubic  millimetre  in  the  thirty-six 
cases  of  Table  VII.,  B  (the  lymphatic  cases  being  excluded), 
was  438,000  at  the  time  when  the  cases  first  came  under  obser- 
vation. The  highest  count  in  this  series  is  1,072,222  and  the 
lowest  98,000. 

Cases  are  on  record  in  which  the  white  cells  were  actually 
more  numerous  than  the  red.  The  average  ratio  in  my  series  is 
about  one  white  to  seven  red.  The  highest  ratio  is  1 :  2,  and 
the  lowest  1 :  37.  It  is  best  to  use  the  "  red  counter"  with  a 
dilution  of  1 :  200  in  counting  the  white  cells,  otherwise  they 
are  often  too  crowded  for  convenience.  The  hsematokrit  is 
useful  in  this  disease  and  in  any  condition  where  the  white  cells 
are  much  increased,  not  to  supersede  the  Thoma-Zeiss  or  to 
give  us  the  absolute  number  of  cells,  but  for  comparative  obser- 
vations as  to  the  length  of  the  column  of  white  cells  from  day  to 
day  in  a  given  case.  Hayek  '  has  shown  that  the  count  of  leu- 
cocytes may  vary  enormously  in  a  very  few  hours ;  e.g.,  10  A.M., 
122,500;  4  P.M.,  235,000;  or  again,  10  A.M.,  730,000;  4  P.M., 
547,500. 

In  the  fresh  specimen  we  notice  that  a  large  proportion  of 
the  white  cells  are  not  amoeboid,  a  point  of  marked  contrast 
with  leucocytosis,  in  which  nearly  all  the  leucocytes  are  amoe- 
boid. This  is  due  to  the  fact  that  the  myelocytes  which  form 
so  large  a  portion  of  the  leucocytes  in  this  disease  possess  little 
if  any  faculty  of  amoeboid  motion.  We  should  expect  there- 
fore to  find  their  nuclei  free  from  the  twists  and  distortions 
1  Hayek:  Wien.  klin.  Woch.,  1897,  No.  20. 


164 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


characteristic  of  the  amoeboid  (polymorphonuclear)  cells.     And 
this  is  in  fact  the  case  (see  below) . 

TABLE  VIII. — MYELOCYTJEMIA  (SPLENIC-MYELOGENOUS  LEUKAEMIA). 


6 

fc 

1 
2 

3 

4 
5 
6 

7 

8 

9 
10 
11 
12 
13 
14 
15 
16 

17 
18 
19 

20 

21 
22 
23 
24 
25 
26 
27 
28 

g 

1 

2,010,000 
1,720,000 

4,125,000 

4,016,000 
4,592,000 

2,960,000 
3,184,000 
3,156,000 
3,400,000 
3,670,000 
3,100,000 
3,080,000 
2,520,000 

4,016,000 

2.792,000 
2,715,000 
2,256,000 
4,288,000 
2,921,600 
3,010,000 
2,996,000 
4,800,000 
3,060,000 
2,016,000 
2,576,000 
2,448,000 
2,120,000 

2,528,000 
5,120,000 
5,000,000 
4,800,000 

I 

i 

-2 
£ 

716,000 
732,000 
708,000 
253,900 
200,000 
646,000 
448,000 

175,800 
264,000 
276,000 
111,000 
183,090 
430,000 
405,000 
510,000 
528,000 
570,000 
560,000 
800,000 
26,000 
139,600 
394,000 
340,000 
213,000 
492,800 
188,000 
134,400 
220,500 
274,000 
260,000 
748,000 
168,800 
190,000 
188,600 
159,000 
134,000 
137,800 
138,000 

PERCENTAGE. 

Normoblasts  seen  while 
counting  them. 

Megaloblasts  seen  while 
counting  them. 

Date. 

d 

M 
W 

§  1  Polymorphonuclear 
neutrophiles. 

1-1  Small  lymphocytes. 

cc 

1 

1 

1 

j>> 
10 

1 

1 

4 

1 
| 

>> 
g 

42 

1 
1 

CO 

1 

1 

"fl 
1—  1 

3.8 

Many 

Many 

Many 

Nov.  1st,  1897.1 
Nov.  3d,  1897. 
Nov.  12th.  1897. 
July  16th,  1895. 
July  25th,  1895. 
Jan.  21st.  1897. 
Feb.  8th,  1897. 
Feb.  17th,  1897. 
July  15th,  1897. 
July  29th,  1897. 
Aug.  5th,  1897. 

Aug.  10th,  1896. 
Aug.  31st,  1896. 
Jan.  22d,  1896. 
Jan.  22d,  1896.2 
Jan.  23d,  1896. 
Jan.  24th,  1896. 
June  4th,  1894. 
Aug.  10th,  1894. 
April,  1893.    Later 
the    count   of 
leucocytes    was 
normal  for  sev- 
eral months. 

Jan.  22d.  1896. 
June,  1897. 

Feb.  22d,  1896. 
Feb.  25th,  1896. 
Feb.  28th,  1896. 

55 

60 

42 
38 
in 
35 

48 
40 
50 

56.5 
46 
46.6 
17 

7 
1.5 
1.4 
3 

4.5 
14.5 
10.4 
11 

4 
1.5 
2.2 

19 

28 
33.5 
36.7 
49 

Many 

Many 

3 
2 
3 

13 

1 
0 
0 
31 

27.2 
31 

10.5 
15 

26 
8 

3 
5 

25 
32 

Many 

Many 

72.2 
51 

2 
.6 

3.6 
2 

2 

4 

17.4 
42.4 

Many 

Many 

5 

9 

58 

55 

5 

4 

4 

34 

Many 

Many 

87 

41 

42 

45 

78 

50.4 
44 
62.3 
53.8 
61 
37 
46 
62 
33 
26 
46 
45 

74.2 

18.9 
1.5 
3.8 
2.2 
3 
23 
1.5 
1.5 
10 
8 
2 
3 

4 

0.2 
1 
1.8 
2.8 
0 
6 
0.5 
1 
11.5 
1 
0.5 
3 

4 

6.1 
2.5 
1.8 
14.4 
3 
8 
4 
2.5 
3 
5 
1.5 
3 

2.8 

24.4 
51 

30.3 
18 
33 
26 
48 
33 
42.5 
60 
50 
46 

15 

8.8 

4 

1 

;; 

61 
32 

49.6 
30 
54 

6 
4 
3.6 
10 
8 
24.5 
4 
0 
5 

6 

2.2 

4 
2.2 
5 
0 
5 
4 
1.5 
3 

2.5 
5 

6 
5 
5 
1.5 
28 
3.7 
1 

28 
55 
38.6 
45 
34 
27.5 
28 
36 
47 

10 

1.5 
2 

36 
57.5 
42 

* 

Av. 

3,120,000 

348,000 

52 

46 

4.6 

5.1 

35 

5 

1  Many  cells  on  border-line  between  large  lymphocytes  and  myelocytes 
and  between  these  and  polymorphonuclear  neurophiles. 

2  Cerebral  hemorrhage.     Death  January  25th,  1896. 


LEUKEMIA.  165 

With  or  without  the  influence  of  therapeutic  agencies  the 
white  cells  may  fall  gradually  to  normal  and  remain  there  for 
some  time,  the  patient  feeling  greatly  improved.  Such  a  case 
occurred  under  my  observation,  and  the  patient,  a  washer- 
woman, went  back  to  work  and  afterward  passed  through  an 
attack  of  lobar  pneumonia  in  safety. 

At  such  a  time,  when  no  increase  in  the  white  cells  is  pres- 
ent, we  should  never  suspect  leukaemia,  seeing  the  case  for  the 
first  time,  unless  we  chance  to  make  a  differential  count;  then 
the  characteristic  qualitative  changes  (see  below)  would  be  seen. 

QUALITATIVE  CHANGES. 
1.  Myelocytes. 

The  enormous  number  of  myelocytes  is  the  chief  point  of 
interest.  The  average  in  my  28  cases  was  35  per  cent  (see 
Table  VIII.),  rising  in  one  case  as  high  as  60  per  cent  and  only 
twice  falling  lower  than  20  per  cent. 

Taking  the  average  total  number  of  leucocytes  as  428,000  per 
cubic  millimetre,  the  absolute  number  of  myelocytes  would  be 
over  150,000  per  cubic  millimetre.  So  far  as  I  am  aware  the 
highest  count  of  myelocytes  in  any  other  disease  is  that  men- 
tioned on  page  306  in  a  case  of  malignant  disease,  namely,  4,514 
per  cubic  millimetre.  The  contrast  is  sufficiently  striking.  I 
wish  to  insist  upon  this  point,  namely,  that  the  blood  of  splenic- 
myelogenous  leukaemia  is  absolutely  peculiar  and  characteristic, 
and  could  not  be  confused  with  that  of  any  other  disease.  Cer- 
tain writers  of  late  years  have  concluded  that  because  myelo- 
cytes do  occur  in  a  great  variety  of  diseases  as  well  as  in  leu- 
kaemia, therefore  there  is  nothing  peculiar  about  the  blood  of 
the  latter  affection.  It  would  be  as  logical  to  say  that  because 
albumin  and  casts  occur  occasionally  in  the  urine  of  persons 
practically  well,  therefore  there  is  nothing  characteristic  about 
the  urine  of  acute  nephritis. 

Between  the  largest  number  of  myelocytes  ever  recorded  in 
any  disease  other  than  leukaemia,  and  the  smallest  number  ever 
found  in  the  latter  disease,  there  is  as  great  a  difference  as  there 
is  between  the  minute  traces  of  sugar  to  be  found  in  normal 
urine  and  the  marked  glycosuria  of  diabetes  mellitus. 


166  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

At  the  first  glance  the  stained  specimen  of  leuksemic  blood 
seems  to  be  composed  mostly  of  myelocytes,  but  this  is  because 
they  are  on  the  average  so  much  larger  than  the  other  forms  of 
white  cells,  which,  being  packed  away  in  the  interstices  between 
the  large  myelocytes,  do  not  appear  prominently  at  first 
sight. 

Although  (as  just  mentioned)  the  average  size  of  the  mye- 
locytes is  greater  than  that  of  any  other  kind  of  leucocyte,  there 
is  a  great  range  of  variation  in  their  size,  and  some  are  hardly,  if 
at  all,  larger  than  a  red  cell.  (This  is  equally  true  of  the  mye- 
locytes as  seen  in  the  bone  marrow.  See  above,  page  71 ,) 

The  individual  characteristics  and  variations  in  the  myelo- 
cytes have  been  already  sufficiently  described  on  page  69. 


2.  Polymorphonuclear  Cells. 

Although  absolutely  the  number  of  these  cells  is  greatly  in- 
creased, the  number  in  each  1,000  leucocytes  is  considerably 
diminished.  The  average  percentage  in  the  28  cases  of  Table 
VIII.  is  46,  the  figures  ranging  between  17  and  72  per  cent. 

The  individual  cells  show  a  much  greater  range  of  variation 
in  size,  staining  properties,  and  the  size  and  shape  of  the 
nucleus  than  in  any  other  condition.  In  most  forms  of  leu- 
cocytosis,  for  example,  one  adult  cell  looks  very  much  like 
another,  but  in  this  form  of  leukaemia  we  are  often  struck  by— 

(a)  Very  small  cells  or  very  large  cells. 

(b)  Dark  stained  or  very  pale  stained  cells. 

(c)  Unusual  shapes  in  the  nuclei. 

Besides  these  variations  we  often  see  cells  apparently  be- 
longing to  this  type,  but  whose  protoplasm  shows  no  color  what- 
ever. Such  a  cell  is  figured  to  the  right  of  Plate  II.,  Fig.  1. 
Other  cells  show  a  few  granules  scattered  about  against  a  per- 
fectly white  background.  The  outer  rim  of  the  cell  is  usually 
stained  faintly,  so  that  we  can  hardly  make  out  its  outline.  Such 
cells  usually  contain  basophile  granules  beside  tlie  neutrophile. 

(d)  There  are  always  some  cells  on  the  border-line  between 
the  polymorphonuclear  and  the  myelocyte,  and  in  regard  to 
which  decision  must  be  arbitrary.     We  cannot  help  getting  the 


LEUKEMIA.  167 

impression  that  at  any  rate  in  this  disease  the  two  varieties  are 
only  different  stages  in  the  development  of  the  same  cell. 

(e)  More  than  one  kind  of  granule  is  sometimes  seen  in  the 
protoplasm,  i.e.,  eosinophilic  or  basophilic  as  well  as  neutro- 
philic. 

5.  Lymphocytes. 

It  is  here  that  the  greater  relative  diminution  occurs,  to  make 
room  for  the  incursion  of  the  myelocytes.  In  percentages  they 
are  reduced  from  their  normal,  20  to  30  per  cent,  to  an  average 
of  10.6  per  cent,  as  in  leucocytosis.  But  still  their  absolute 
number  is  always  increased.  Thus  the  lowest  percentage 
present  in  Table  VIII.  (namely,  two  percent)  would  mean  8,760 
out  of  the  average  438,000,  the  total  leucocyte  count  per  cubic 
millimetre,  and  8,760  is  three  or  four  times  as  many  lym- 
phocytes per  cubic  millimetre  as  are  present  in  normal  blood. 

The  proportion  of  large  and  small  forms  among  the  lym- 
phocytes varies  a  great  deal.  Sometimes  the  lymphocytes  of 
this  form  of  leukaemia  do  not  differ  from  those  of  normal  blood, 
but  in  most  cases  we  find  one  or  more  of  the  following  atypical 
varieties : 

(a)  Lymphocytes  with  a  protoplasm  so  darkly  stained  that 
it  is  difficult  to  distinguish  them  from  myelocytes.     Indeed  in 
some  cases  where  hints  of  a  granular  look  appear  in  the  violet- 
stained  rini  we  find  it  impossible  to  be  sure  whether  we  are  deal- 
ing with  a  large  lymphocyte  or  a  myelocyte.     The  personal 
equation  alone  decides. 

(b)  Cells  like   lymphocytes  except  that  they  contain  from 
three  to  ten  widely  separated  granules  of  one  or  more  varieties 
(basophilic,  acidophilic,  or  neutrophilic). 

4.  Eosinophiles. 

Like  all  the  other  varieties  these  are  absolutely  much  in- 
creased. Relatively — by  percentages — they  may  or  may  not  be 
so.  In  my  series  they  ranged  from  1.5  to  28  per  cent,  averag- 
ing 5.1  per  cent,  a  slight  increase  over  the  normal. 

Many  writers,  wrongly  interpreting  Ehrlich's  observations 
on  this  point,  have  stated  that  an  increased  percentage  of  eosino- 
philic cells  was  the  distinguishing  mark  of  leukaemia,  and  even 


168  SPECIAL   PATHOLOGY    OF   THE    BLOOD. 

recent  writers  (e.g.,  Gilbert,  Strumpell)  continue  to  repeat  this 
false  statement. 

The  cell  characteristic  of  splenic-myelogenous  leukcemia  is  not 
the  eosinophile  but  the  myelocyte. 

We  distinguish  several  types  of  eosinophiles  in  leuksemic 
blood. 

(a)  Ordinary  (polymorphonuclear)  eosinophiles. 

(b)  Eosinophilic  dwarf  cells. 

(c)  Eosinophilic  myelocytes. 

(a)  Needs  no  comment;  (b)  is  simply  a  very  small  cell  with 
eosinophilic  granules ;  sometimes  such  cells  are  not  over  5  P-  in 
diameter.  They  are  not  uncommon  in  this  form  of  leukaemia 
and  are  very  rare  in  any  other  disease.  The  same  is  true  of  (c), 
the  eosinophilic  myelocytes  which  are  very  rare  in  any  other 
disease,  except  pernicious  anaemia,  where  they  are  occasionally 
seen. 

These  cells  are  like  myelocytes  except  that  their  granules 
are  eosinophilic  instead  of  neutrophilic  (see  Plate  I.  and  Plate 
II.).  They  are  found  in  the  marrow  in  considerable  numbers 
and  constitute  the  majority  of  the  eosinophilic  cells  seen  in  this 
form  of  leukaemia.  Occasionally  we  see  eosinophiles  with  a  few 
basophilic  or  neutrophilic  granules  as  well. 

5.  Basopliiles. 

(a)  The  lymphocytes  may  contain  basophilic  granules  as  in 
any  ordinary  blood. 

(b)  Certain  of  the  myelocytes  contain  fine  basophilic  granules 
in  addition  to  their  usual  neutrophilic  granules. 

(c)  "  Mastcellen"   or   coarsely  granular    basophiles,   usually 
with  a  trilobed  nucleus,  are  almost  always  seen  in  specimens 
stained  with  dahlia  or  methylene  blue.     With  the  triple  stain 
their  protoplasm  is  nearly  unstained,  but  usually  a  number  of 
round  white  spots  can  be  made  out  against   a  faintly  stained 
background.      These  are  the  basophilic  granulations.      Mast- 
cells  make  up  from  one  to  ten  per  cent  of   the  leucocytes    in 
most  cases  of  myelocytaemia. 


LEUKAEMIA.  169 

6.  Polymorphous  Condition  of  the  Blood. 

Weiss  has  rightly  insisted  on  the  fact  that  in  this  type  of 
leukaemia  the  blood  preparations  show  a  very  polymorphous 
condition,  that  is,  there  are  no  fixed  types,  but  every  variety 
shades  through  intermediate  forms  into  some  other  variety.  No 
two  cells  are  alike.  Precisely  the  same  conditions  obtain  in 
the  normal  marrow,  and  we  can  scarcely  resist  the  impression 
that  in  this  form  of  leukaemia  we  see  in  the  blood  unfinished 
cells  of  various  kinds  which  usually  do  not  appear  in  the  circu- 
lating blood. 

As  Charcot-Leyden  crystals  have  no  diagnostic  value  and 
are  not  peculiar  to  any  disease,  no  description  of  them  will  be 
given  here.  They  appear  to  be  present  wherever  eosinophiles  are 
plentiful,  e.g.,  in  asthma,  gonorrhoea,  in  the  bone  marrow,  etc. 

Kanthack  considers  that  a  diminution  in  eosinophiles  (pro- 
gressive) is  a  bad  prognostic  si^n.  During  remissions,  when 
the  leucocyte  count  may  fall  to  normal,  the  percentage  of 
myelocytes  remains  large  and  the  diagnosis  could  usually  be 
made  even  if  we  saw  the  case  then  for  the  first  time.  This 
I  have  observed  in  two  cases,  and  Thayer  has  had  the  same  ex- 
perience. 

II.   LYMPH^EMIA. 

(Lymphatic  Leukaemia.) 

Although  Fraenkel  once  maintained  that  all  cases  of  lym- 
phatic leukaemia  are  acute,  and  that  therefore  the  difference  be- 
tween the  various  forms  of  the  disease  rests  simply  on  the 
rapidity  of  the  process  in  the  blood  and  clinically,  there  is  no 
doubt  that  chronic  lymphatic  leukaemia  exists. 

Fraenkel  was  enabled  to  maintain  his  position  only  by  ex- 
tending the  term  acute  to  cover  all  cases  whose  symptoms  last 
not  more  than  four  months.  Six  weeks  is  the  limit  agreed  upon 
by  most  other  observers. 

The  writer  has  watched  five  cases  of  typical  lymphatic  leu- 
kaemia for  periods  of  from  seven  months  to  two  years.  One  was 
as  little  sick  as  any  case  of  leukaemia  that  I  have  ever  seen,  and 
came  over  thirty  miles  from  time  to  time  to  report  at  the  Out- 
Patieut  department.  His  blood  showed  little  variation  from  the 
following  figures:  Ked  cells,  2,300,886;  white  cells,  112,000. 


170  SPECIAL    PATHOLOGY    OF    THE    BLOOD. 

The  differential  count  always  showed  the  overwhelming  ma- 
jority (over  ninety  per  cent)  of  small  lymphocytes  characteristic 
of  the  disease.  The  lymph  glands  were  all  much  enlarged,  the 
spleen  just  palpable.  The  patient  kept  about  his  work  as  a 
gardener  for  over  two  years.  Grawitz  has  watched  a  similar 
case  for  over  four  years. 

The  blood  of  acute  lymphaemia  differs  as  a  rule  in  many 
respects  from  that  of  chronic  cases.  These  differences  will  be 
referred  to  later  on. 

RED  CELLS. 

The  count  of  red  cells  is  often  somewhat  lower  than  in  the 
splenic-myelogenous  form  of  the  disease,  averaging  2,730,000 
in  my  cases.  In  acute  cases  it  is  usually  very  low  and  the  an- 
aemia progresses  rapidly.  In  chronic  cases  the  red  cells  behave 
about  as  in  myelocythaemia,  except  as  regards  nucleated  forms. 

Here  the  point  of  interest  is  the  comparative  rarity  of  nu- 
cleated red  cells,  the  abundance  of  which  is  so  marked  a  feature 
of  splenic-myelogenous  leukaemia.  They  follow  the  grade  of 
anaemia  present.  Cases  occurring  in  children  show  more  abun- 
dant nucleated  corpuscles  (the  same  is  true  of  all  leukaemia  in 
children)  than  those  occurring  in  adults',  and  the  megaloblasts, 
usually  scanty,  may  equal  the  number  of  normoblasts.  In 
very  acute  cases  the  number  of  nucleated  forms  is  greater  and 
may  be  as  great  as  in  myelocytaemia.  Two  cases  recently 
reported  by  Herrick  x  exemplify  this. 

WHITE  CELLS. 
Quantitative  Changes . 

As  a  rule  the  numerical  increase  is  not  nearly  so  marked  as 
in  the  splenic-myelogenous  form.  The  average  ratio  of  white 
to  red  cells  is  about  1 : 50  instead  of  1:7,  and  we  rarely  see 
counts  reach  the  height  common  in  the  other  form  of  the  disease. 
The  highest  count  of  my  series  was  1,480,000  at  the  patient's 
first  visit,  and  the  lowest  30,000,  the  average  being  141,000  as 
compared  with  438,000  in  the  other  form.  These  figures  refer 
to  uncomplicated  cases. 

1  Journal  of  the  American  Medical  Association,  July  24th,  1897. 


PLATE  III. 

(a)  Chronic  Lymphcemia  with  Excess  of  Small  Lymphocytes. 

One  polymorphonuclear  cell  is  present.  All  the  rest  are  lymphocytes 
and  exemplify  the  variations  in  the  morphology  of  the  cell  occurring  in 
this  and  other  diseases  as  well  as  in  health,  e.g.,  variations  in  the  stain- 
ing of  the  protoplasm  and  nucleus,  indentation  and  even  division  of  the 
nucleus. 

Note  that  the  scale  of  the  whole  of  Plate  III.  is  larger  than  in  the  other 
plates  (see  scale  of  p.) . 

(b)  Acute  Lymphcemia  with  Excess  of  Large  Lymphocytes. 

Note  the  lack  of  chromatin  in  both  nuclei  and  protoplasm  of  large 
lymphocytes.  The  plasma  around  them  or  their  extreme  edge  took  most 
of  the  stain.  The  brown  tint  of  the  red  cells  is  due  to  underheating. 
Compare  the  colors  with  those  in  the  figure  above  (a)  in  which  the  prep- 
aration was  properly  heated. 


Examination  of  the  Blood. 


Lymphatic  Leucaemia 

a.  Small  Lymphocytes  in  excess 

b.  Large 


Scale  of  |A 


R.  C.  Cabot  fee. 


Lith.  Anst.  v.  B.   \.  Kunke,  Leipzig 


LYMPHATIC    LEUKAEMIA. 


171 


Qualitative  Changes. 

1.  Lymphocytes  (small  forms,  large  forms,  or  a  mixture)  make 
up  usually  over  ninety  per  cent  of  all  the  leucocytes  present.  In 
some  cases  they  are  all  nearly  of  one  size,  while  in  others  we 
find  every  gradation  from  the  smallest  to  the  largest,  so  that  it 
is  absolute^  futile  to  attempt  to  separate  them  into  "  large"  and 
"small."  Four  of  my  cases  were  made  up  wholly  of  the  small 
forms  all  under  10  //  in  diameter,  two  were  composed  largely  of 
forms  over  15  v-  in  diameter,  while  six  showed  every  inter- 
mediate size. 

TABLE  IX.— LYMPHATIC  LEUKEMIA. 


No. 

Red  cells. 

White 
cells. 

Per  cent 
haemoglobin. 

Small 
lymphocytes.  | 

t 

&f 

1 

Polynuclear 
neutrophiles. 

Eosinophiles. 

Myelocytes. 

Normoblasts. 

Megaloblasts.  | 

Remarks. 

1  
2 

4,877,000 
91°  000 

132,000 
23  000 

17 

75.8 
15 

16. 

82 

4.6 
2  4 

1.6 
1 

2. 

5 

4 

1 

Subacute  ;     ten 
weeks. 
Jan    24th   1896 

1  440  000 

43,600 

?S 

Jan.    26th,    1896 

1,336,000 
1  100  000 

92,000 
120000 

20 

25.4 

73.2 

.5 

.1 

.8 

3 

1 

Acute  ;  two  weeks. 
Jan.  27th. 
Jan.    28th.     Death- 

3        

3,000,000 

31,600 

685 

28. 

3.2 

0 

autopsy. 
April  3d,  1896. 

3  500  000 

31  500 

55 

78 

156 

56 

0 

fi 

April  5th,  1896 

3,608,000 

28,500 
40000 

55 

95.3 

• 

4.3 

.3 

... 

April  6th,  1896. 
April    7th,    1896 

4  700  000 

31,500 
40  000 

95.5 

* 

4. 

.5 

2 

2 

Acute:  five  weeks. 
April  8th,  1896. 
April  12th  1896 

3  100  000 

3  400 

39 

52 

9 

April   22d   (sepsis 

800 

94  7 

* 

53 

semicomatose). 
\pril  29th      Death 

4  

2,960,000 

1,480,000 

87.9 

12. 

.1 

IB 

March   21st    1897 

5... 

4  160  000 

80000 

80  5 

2  1 

172 

0 

Chronic. 
Oct      26th     1896 

2,768,000 

77,500 
51,800 

50 

88.7 

1.6 

9.4 

.2 

.1 



Chronic. 
Nov.  5th,  1896. 
Nov.  7th    1896 

90  4 

1  4 

g 

2 

Nov    15th   J896 

79,500 

Nov     17th       Died 

6... 

3  520,000 

64,000 

60 

94 

6 

December,  1897. 

7 

94 

# 

5  7 

87 

8  
9  

97.9 
862 

7. 

1.4 
9  8 

.8 

2 

•  • 

Acute. 

10 

72 

28 

11... 

99  6 

'*  ' 

4 

Few 

History  unknown 

12... 

92  2 

* 

78 

13  

700,000 

600,000 

10 

998 

* 

8 

3 

2,500  cells  counted. 

Average. 

2,900,000+ 

59,000+ 

40 

80.2 

15. 

4.2 

.2 

.4 

*  Large  and  small  forms  counted  together  on  account  of  the  impos- 
sibility of  differentiating  them  in  these  cases. 


172  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

In  acute  cases,  where  the  large  cells  usually  predominate,  the 
staining  is  often  very  faint  throughout  the  nucleus  and  proto- 
plasm (see  Plate  III.,  6),  so  that  at  first  sight  we  should  think 
something  was  wrong  with  our  technique.  Other  forms  of  leu- 
cocytes in  the  same  preparation,  however,  will  stain  normally, 
showing  that  the  trouble  is  in  the  lymphocytes  and  not  in  the 
technique.  These  large  lymphocytes  are  identical  in  their  ap- 
pearance with  those  found  at  the  "  germ  centres"  of  all  adenoid 
tissue,  and  probably  are  the  mother  cells  of  the  small  lym- 
phocytes. Benda  has  termed  them  "lymphogonien."  They 
have  often  been  mistaken  for  myelocytes,  from  which  they  are 
to  be  distinguished  by  the  absence  of  any  neutrophile  granula- 
tion. They  often  show  evidences  of  degeneration  (see  above, 
page  63).  The  protoplasm  may  be  entirely  unstained  as  in 
most  of  the  cells  in  Plate  III.,  b,  or  it  may  stain  pale  gray 
or  pink.  In  other  specimens,  especially  those  of  the  small- 
cell  type  (Plate  III.,  a)  the  lymphocytes  stain  well.  Their 
nuclei  are  frequently  indented  or  even  divided  in  two  (this 
occurs  also  in  normal  blood,  but  less  often) . 

Fraenkel  believes  still  that  lymphaemia,  though  not  always 
acute,  is  usually  so,  and  that  if  a  chronic  case  takes  on  acute 
symptoms  the  blood  becomes  more  lymphsemic,  while  if  a  case 
starts  acute  and  becomes  chronic  the  lymphocytes  decrease. 
Thus  in  a  case  reported  by  v.  der  Wey  1  a  chronic  myelo- 
'cytsemia  six  weeks  before  death  began  to  have  fever,  hemor- 
rhages, great  increase  in  the  total  leucocyte  count  and  in  the 
ansemia.  No  complication.  The  lymphocytes  increased  30  per 
cent,  and  the  polymorphonuclear  neutrophiles  dropped  from  30 
to  3  per  cent. 

Gerhardt 2  watched  a  case  which  began  acutely  with  a  large 
percentage  of  large  lymphocytes  and  then  became  chronic  with 
a  predominance  of  small  lymphocytes. 

In  acute  cases  Litten 3  has  noticed  fatty  degeneration  in  the 
leucocytes. 

The  following  figures  illustrate  the  influence  of  a  septicaemia 
(from  suppurating  cervical  glands)  which  ended  the  life  of  No. 
3  in  the  above  Table  X. 

1  Deut.  Arch,  f .  klin.  Med. ,  vol.  57. 
2 15th  Cong.  f.  innere  Med.,  1897. 
s  llth  Cong,  f.  innere  Med.,  1893. 


LYMPHATIC   LEUKEMIA. 


173 


Date. 

Number 
of  leucocytes. 

Percentage  of 
lymphocytes. 

April    3d                           ...            

31,600 

96.5 

4th                           

31,000 

6th                    

28,505 

93.6 

8th  

44,000 

10th  

31,500 

95.5 

12th  

40,000 

13th                       

Sepsis  began. 

20th     ...       

5,661 

21st    

4,000 

22rl  

3,400 

92. 

24th                                           .    . 

3,222 

28th                                   

800 

"      29th                      

471 

94.7 

Death  on  the  29th. 

Zeissl's  case,  also  of  the  lymphatic  form,  showed  the  follow- 
ing: 


Date. 

White  cells. 

Percentage  of 
lymphocytes. 

Percentage  of 
adult  cells. 

September    9th  . 

80,000 

96. 

4. 

24th  

113,000 

26th  

119,000 

"          29th 

122  000 

97  8 

2 

October   6th  .  . 

140  000 

9th  

Pneumonia  began 

99. 

1 

10th  

119  000 

llth  

98  000 

12th  

68,500 

13th  

43,500 

88.7 

11.3 

14th  

50,000 

15th  

9,350 

85.4 

14.6 

16th  (A.M.)  
16th  (P.M.)  

133,200 
172,000 

75. 

25. 

Polymorphonuclear  neutrophiles  are  often  so  scarce  that  one 
has  to  look  through  several  thousand  leucocytes  before  finding 
one.  There  is  nothing  abnormal  about  them.  Eosinopliiles 
and  myelocytes  are  equally  rare. 

Summary. 

The  leading  characteristics  of  leuksemic  blood  are  as  follows : 
(a)  Myelocytcemia. 

1.  Red  cells  about  3,000,000,  nucleated  forms  very  numerous. 

2.  White  cells  about  450,000,  of  which 

3.  Myelocytes  form  about  thirty  per  cent. 


174  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

4.  Every  possible  form  of  cell  intermediate  between  the  ordi- 
nary varieties  is  to  be  seen.     ("Polymorphous  blood.") 

(b)  Chronic  Lymplicemia. 

1.  Red  cells  about  3,000,000  or  lower;  nucleated  forms  rare. 

2.  White  cells  about  100,000  or  lower,  of  which 

3.  Small  lymphocytes  usually  form  over  ninety  per  cent. 

4.  Myelocytes  and  eosinophiles  very  scanty. 

(c)  Acute  Lymphcemia. 

1.  Red  cells  much  diminished;    nucleated  forms  not  infre- 
quent. 

2.  Large  forms  of  lymphocytes  usually  predominate;  many 
of  them  often  show  signs  of  degeneration. 

3.  Neutrophiles  and  eosinophiles  very  scanty. 

Diagnostic   Value. 

Leukaemia  is  distinguished  by  the  blood  examination  from 

1.  Hodgkin's  disease:  (a)  splenic,  (b)  glandular. 

2.  Tumors  of  the  spleen  and  vicinity  (e.g.,  kidney  or  retro- 
peritoneal  glands). 

3.  Enlargements  of  the  lymphatic  glands  from  tuberculosis, 
syphilis,  malignant  disease. 

4.  Hydronephrosis. 

5.  Huge  leucocytosis  from  any  cause. 

6.  Chronic  malaria. 

7.  Amyloid  disease. 

1.  Leickcemm    and    Hodgkin's    disease    (lymphadenoma    or 
pseudo-leukaemia) .     The  pathology  of  the  two  diseases  is  iden- 
tical but  for  the  blood  count.     In  Hodgkin's  disease  the  blood 
is  normal,   or  shows  only  a  moderate  anaemia  or  leucocytosis 
(poly  morphonuclear  cells  alone  increased) ,  and  the  diagnosis  is 
easily  made. 

2.  Tumors  of  the  spleen  and  epecially  of  the  kidney  are  very 
apt  to  be  mistaken  for  leukaemia.     Within  a  year  I  have  been 
asked  to  examine  the  blood  in  three  cases  of  "leukaemia,"  all  of 
which  turned  out  to  be  malignant  disease  of  the  kidney.     In  all 
of  these  there  was  a  large  tumor  resembling  the  spleen  in  the 
left  hypochondrium  and  a  very  large  increase  of  white  cells. 
In  two  of  them  the  blood  was  examined  fresh  and  the  great 
number  of  white  cells  in  the  slide  taken  as  evidence  confirmatory 
of  leukaemia.      The  stained  specimen,   however,    showed  only 


LYMPHATIC   LEUKAEMIA. 


175 


marked  leucocytosis  with  ninety  per  cent  of  adult  cells  of  the 
ordinary  type  and  no  myelocytes.  Other  large  tumors  of  this 
region  showed  similar  results.  Occasionally  cases  of  leukaemia 
with  numerous  metastases  are  described  as  "  sarcomatosis, "  and 
then  it  is  asserted  that  the  blood  of  leukaemia  is  identical  with 
that  of  sarcoma.  The  source  of  the  mistake  is  obvious. 

3.  Adenitis   with    hyperplasia    due   to    tuberculosis    shows 
usually  normal  blood '   and  is  thus  easily  distinguished  from 
leukaemia.     Leucocytosis  is  often  present  in  syphilitic  cases  and 
still  more  marked  in  those  due  to  cancer  or  sarcoma,  but  the 
counts  rarely  reach  30,000  and  myelocytes  are  absent  or  very 
scanty. 

4.  One  case  of  hydronephrosis,  in  which  the  distention  of  the 
sac  was  so  great  that  it  presented  as  a  hard,  solid  tumor  on  the 
right  hypochondrium,  was  taken  for  leukaemia  by  a  competent 
observer  some  years  ago.     The  normal  blood  examination  re- 
vealed the  mistake,  and  excluded  also  malignant  disease  in  all 
probability.     The  diagnosis  was  only  reached,  however,  at  the 
autopsy. 

5.  Huge  leucocytosis   in  pneumonia  or   malignant  disease 
may  often  cross  the  old  boundary  line  of  100,000  white  cells, 
beyond  which  none  but  leukaemic  cases  were  supposed  to  ven- 
ture.    The  differential  count  sets  us  right  instantly,  showing 
ninety  per  cent  or  so  of  the  increase  to  be  made  up  of  ordinary 
polymorphonuclear  leucocytes. 

6  and  7.  The  large  spleen  and  cachectic  appearance  asso- 
ciated with  chronic  malaria  and  long-standing  suppurations  may 
be  easily  distinguished  from  leukaemia  by  the  absence  of  any- 
thing more  than  anaemia  and  leucocytosis  in  the  blood. 


Red  cells. 

White  cells. 

Lympho- 
cytes. 

Poly- 
nuclear 
leucocytes. 

Myelo- 
cytes. 

Nucleated 
red  cells. 

Leukaemia  (splenic- 
myelogenous). 
Leukaemia   (  1  y  m  - 
phatic). 
Hodgkin's  disease  .  . 

Tumors  of  or  near 
the  spleen. 
Leucocytosis  in  gen- 

About 
3,000,000 
About 
3,000,000 
About 
normal. 
Usually 
diminished. 

450,000  ± 
100,000  ± 
7,500  ± 
20,000  to 
40,000  ± 
May  be  over 

About   7.6 
per  cent. 
About  96 
per  cent. 
Normal. 

Greatly 
decreased. 
Greatly 

About  50 
per  cent. 
About  3 
per  cent. 
Normal. 

Greatly 
increased, 
Greatly 

About  37 
per  cent. 
Absent. 

Absent. 

Few  if 
any. 
Few  if 

Very 
numerous. 
Rare. 

Absent. 
Few. 
Few  at 

eral. 
Chronic  malaria.  .  .  . 

Amyloid  disease  
Hydronephrosis  

.  Much 
diminished. 
Usually 
diminished. 
Normal. 

100,000 
Somewhat 
increased. 
Usually 
increased. 
Normal. 

decreased. 
Usually 
increased. 
Usually 
decreased. 
Normal  or 
decreased. 

increased. 
Usually 
decreased. 
Usually 
increased. 
Normal. 

any. 
Few  if 
any. 
Absent. 

Absent. 

times. 
Few. 

May  be  a 

few. 
Absent. 

1  Sometimes  marked  leucopenia. 


176  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 


EFFECT  OF  INTEBCUBBENT  INFECTIONS. 

There  are  on  record  about  thirty  cases  in  which  leukaemia 
(acute  or  chronic)  has  been  complicated  with  some  intercurrent 
infection,  with  marked  effect  upon  the  blood  in  all  but  one. 
This  single  case  was  an  acute  rheumatic  arthritis  reported  by 
Bichter  in  the  discussion  of  Fraenkel's  article  in  the  Deutsche 
medicinische  Wocliemchrift  for  1895  (Nos.  39,  43,  and  45),  p. 
639.  Here  the  blood  remained  unchanged. 

Miiller's  '  case  of  lymphatic  leukaemia  was  complicated  by  a 
septicaemia,  and  the  count  of  white  cells  rose  from  180,000  to 
400,000  per  cubic  millimetre,  with  a  marked  increase  in  the  per- 
centage of  polymorphonuclear  cells.  Here  was  a  genuine  leu- 
cocytosis  added  to  a  leukaemia. 

With  the  exception  of  these  two  cases,  all  those  hitherto 
published  have  shown  a  marked  progressive  decrease  in  the  total 
number  of  leucocytes  without  any  change  in  the  percentages  of 
the  different  varieties  in  twelve,  while  eight  showed  like  Miiller's 
an  increased  percentage  of  the  polymorphonuclear  cells  despite 
the  decrease  in  the  total  leucocyte  count. 

Marischler  2  in  a  case  of  lymphatic  leukaemia  with  cancer  of 
the  kidneys  found : 

1.  At  First.  2.  Later. 

Red  cells 3,450,000  2,400,000 

White  cells 96,000  48,000 

Haemoglobin 50     per  cent.          30    per  cent. 

Polymorphonuclear  cells 15.6        "  57.5 

Small  lymphocytes 83.3        "  40 

Large  lymphocytes 1.8       "  1.6 

Eosinophiles 18      "  .16 

Myelocytes .16 

Various  infections — miliary  tuberculosis,  pneumonia,  grippe, 
erysipelas,  abscess  of  kidney,  septic  lymph  glands — alike  de- 
creased the  leucocyte  count.  In  one  case  a  rise  just  before 
death  was  observed. 

Thus  in  Henck's  case  the  leucocytes  fell  from  400,500  to 
89,000,  in  one  of  Miiller's  from  246,900  to  57,300,  in  Kovacs' 
from  67,000  to  17,000,  in  Zeissl's  from  140,000  to  9,350.  I 

'Muller:  Deut.  Archiv  fur  klin.  Med.,  1892,  vol.  50,  p.  47. 
nVien.  klin.  Woch.,  July  23d,  1896. 


LYMPHATIC    LEUKEMIA.  177 

have  already  mentioned  a  case  of  lymphatic  leukaemia  (page  173) 
in  which  the  leucocytes  fell  from  40,000  to  under  500,  this  last 
being  on  the  day  of  death.  In  this  case  the  percentages  of  the 
different  varieties  of  leucocytes  remained  entirely  unchanged. 

Herrick  l  reports  a  case  complicated  by  acute  streptococcus 
infection  in  which  the  white  cells  were  60,000  at  the  time  of 
death.  How  high  they  may  have  been  earlier  is  not  known. 

It  appears,  therefore,  that  when  an  infection  complicates 
leukaemia  we  may  have — 

1.  No  effect  (see  case  of  rheumatic  fever  as  a  complication, 
just  mentioned). 

2.  A  genuine  leucocytosis  on  top,  so  to  speak,  of  the  leu- 
kaemia, with  an  increased  percentage  of  polymorphonuclear  cells. 

3.  A  decrease  in  the  leucocyte  count  with  or  without  an  in- 
crease of  polymorphonuclear  cells.     This  decrease  is  by  far  the 
most  common  result  and  may  go  far  below  normal  as  death  ap- 
proaches. 

Goldschneider 2  found  that  by  the  injection  of  splenic  extract 
and  other  substances  he  could  bring  about  a  similar  diminution 
in  the  number  of  leucocytes,  but  that,  as  in  the  case  of  intercur- 
rent  infections,  this  diminution  was  not  accompanied  by  any  im- 
provement in  the  patient's  condition  and  death  followed  as 
usual. 

Abscesses  occurring  in  leukaemic  patients  are  filled  with  adult 
leucocytes  as  ordinary  abscesses  are,  and  do  not  contain  mye- 
locytes. 

HODGKIN'S  DISEASE. 

(Pseudo-Leukcemia,  Lymphoma). 

The  diagnosis  of  this  disease  is  impossible  without  the  blood 
count.  Its  pathology  is  identical  with  that  of  leukaemia  and 
even  post  mortem  the  two  diseases  are  indistinguishable  so  far 
as  the  lesions  outside  of  the  blood  are  concerned.  Yet  the 
blood  is  in  no  way  peculiar,  but  presents  in  most  cases  all  the 
characteristics  of  the  normal  tissue.  Its  value  is  as  negative 
evidence,  telling  us  in  a  given  case  that  leukaemia  is  absent  even 
though  all  the  other  signs  and  symptoms  may  be  those  of  leu- 
kaemia. 

1  Loc.  cit. 

*  Discussion  of  Fraenkel's  article. 
12 


178  SPECIAL  PATHOLOGY   OF   THE   BLOOD. 

(I.)  Transitions  from  Hodgkin's  disease  to  leukaemia  are  said 
to  have  taken  place  under  the  eyes  of  competent  observers,  but 
they  are  very  rare.  Only  three  such  cases  are  on  record  so  far 
as  I  know,  that  of  Fleischer  and  Penzoldt,1  that  of  Hosier,2  and 
one  reported  by  Senator,3  where  two  sisters  came  under  obser- 
vation, both  suffering  form  Hodgkin's  disease.  One  died  of  it; 
in  the  other  the  blood  changed  to  that  of  leukaemia  before  death.4 

Doubtless  many  of  the  other  cases  supposed  to  exemplify  a 
similar  transition  were  really  cases  in  which  a  leucocytosis  arose 
owing  to  some  inflammatory  complication,  as  not  uncommonly 
occurs  (see  below,  Table  X.). 

From  the  existence  of  these  very  rare  cases  of  a  transition  to 
leukaemia  it  has  been  supposed,  especially  by  French  observers, 
that  Hodgkin's  disease  is  simply  an  early  stage  of  true  leu- 
kaemia and  that  this  would  always  become  apparent  were  it  not 
that  the  patients  die  of  some  intercurrent  disease  before  the 
signs  of  leukaemia  have  time  to  show  themselves  in  the  blood. 
One  difficulty  with  this  view  is  that  there  occur  chronic  cases 
which  last  from  eight  to  ten  years  without  any  change  in  the 
blood.  Another  difficulty  is  that  the  transition  is  in  fact  rare 
despite  the  relative  frequency  with  which  the  disease  is  met 
with. 

(II.)  Undoubtedly  many  cases  diagnosed  as  Hodgkin's  dis- 
ease are  in  fact  cases  of  glandular  hypertrophy  due  to  syphilis 
or  tuberculosis,  and  this  fact  has  led  many  to  the  belief  that  all 
cases  called  Hodgkin's  disease  are  in  reality  only  syphilitic  or 
tubercular  adenitis.  In  a  considerable  number  of  cases,  how- 
ever, tuberculosis  has  been  disproven  by  careful  inoculation  ex- 
periments with  the  glandular  tissue,  and  there  is  no  reasonable 
doubt  that  some  cases  at  any  rate  are  not  due  to  tuberculosis  or 
syphilis.  Probably  the  diagnosis  can  never  be  made  with  ab- 
solute certainty  during  life. 

(III.)  The  frequent  occurrence  of  fever  and  other  symptoms 
characteristic  of  an  infectious  disease  has  led  some  writers  to 
class  it  as  such.  In  a  certain  percentage  of  cases  the  disease 

1  Deut.  Arch,  f .  klin.  Med. ,  vol.  17. 
2Zierassen's  "Handbuch  d.  Path,  and  Therap.,"  vol.  8. 
3Berl.  klin.  Woch.,  1882,  p.  533. 

4  It  is  noteworthy  that  all  these  cases  are  of  some  years'  standing — before 
Ehrlich's  methods  were  much  used. 


HODGKIN'S   DISEASE. 


179 


i  (like  leukaemia)  has  run  an  acute  course,  lasting  not  more  than 
six  weeks  from  the  first  symptom  to  death.  In  some  chronic 
cases  the  same  sort  of  evidence  of  an  infectious  nature  has  been 
brought  forward.  Ulcerations  occur  in  the  mouth  and  intes- 
tine through  which  morbid  products  might  gain  admission. 
Various  bacteria  (pyogenic  and  others)  have  been  found  in  the 
blood  and  tissues  from  time  to  time,  but  numerous  negative 
examinations  for  micro-organisms  are  also  on  record,  and  the 
evidence  is  insufficient  to  establish  the  infectious  nature  of  the 
disease.  None  the  less,  there  is  a  growing  tendency  among  the 
leading  writers  and  observers  in  Germany  and  elsewhere,  to  be- 
lieve that  the  disease  will  ultimately  be  shown  to  be  infectious. 
(TV.)  Meantime  most  surgeons  continue  to  regard  it  as  a 
form  of  sarcoma 'and  to  treat  it  like  malignant  disease. 

The  Blood. 

Whatever  the  nature  of  the  disease,  we  find  in  the  earlier 
stages  of  most  cases  normal  blood  as  will  be  seen  in  Table  X. 
(cases  7  to  23  inclusive). 

As  the  disease  progresses  the  haemoglobin  soon  begins  to 
fall,  later  the  red  cells,  until,  as  at  the  end  of  Case  10  of  the  pres- 
ent series,  the  blood  may  reach  the  severest  grade  of  anaemia. 
In  acute  cases  the  anaemia  may  develop  very  rapidly.  The 
usual  qualitative  changes  characterizing  severe  secondary  anae- 
mia may  be  present. 

TABLE  X. — HODGKIN'S  DISEASE. 


Red 

White 

Per  cent 

X 

cells. 

cells. 

haemo- 

Remarks. 

GO 

globin. 

28 

F. 

5,500,000 

64,000 

75 

Polymorphonuclear  cells,   95  per  cent. 

Lymphocytes,  5  per  cent. 

IT 

3  848  000 

39  200 

48 

A                  TVA»  i     enn        r»                     u 

95.2  per  cent. 

Lymphocytes,  4.  6  per  cent. 

24 

F. 

4,886,000 

32,000 

53 

19 

F 

5,528,000 

22,200 

Diff   200  cells        Polymorphonuclear  cells    86  5 

5,160,000 

25,400 

per  cent. 

Six  weeks  later.  Lymphocytes,  12.    per  cent 
Eosinophiles,       1.5 

19 

M. 

2,480,000 

20,200 

33 

Stained  specimens  normal. 

1  There  are  no  reliable  differentia  between  sarcoma  of  lymph  glands 
and  "benign"  lymphoma  histologically. 

2  Diff.  =  Differential  count  of. 


180 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


TABLE  X.— HODGKIN'S  DISEASE  (Continued). 


Age. 

1 

Red 
cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

37 

-\I 

5,990  000 

13  500 

Polymorphonuclear  cells  95  per  cent 

Lymphocytes,  5  per  cent. 

25 

M. 

5,440,000 

9,500 

59 

Death;  autopsy. 

19 

F. 

5,724,000 

C.,800 

42 

Polymorphonuclear  cells,  60  per  cent. 
Lymphocytes,  40  per  cent. 

Adult. 

M. 

3,652,000 

5,800 

Diff.  300.     Polymorphonuclear   cells,    50.0     per 
cent. 
Lymphocytes,  45.3  per  cent 
Eosinophiles,    1.3 
Myelocytes,       1.7 
Big  spleen,  pallor,  nosebleed,  debility. 

29 

M. 

5,210,000 
3  840000 

5,000 
5,600 

1  000  000 

58 

M. 

2,820,000 

4,800 

60 

Polymorphonuclear  cells,  80  per  cent. 
Lymphocytes,  17  per  cent. 
Eosinophiles,     3 

31 

M. 

4,560,000 

4,000 

5,800 



23 

AI 

4  210  000 

3  332 

Eosinophiles,  4 

M. 

3,800,000 

1,440 

67 

Diff.  500.     Polymorphonuclear    cells,  71.25  per 
cent. 
Lymphocytes,  28.0     percent. 
Eosinophiles,        .75       " 
One  normoblast. 

No 

Diff    200      Polymorphonuclear    cells     63  5   per 

leucocy- 

tosis. 

cent. 
Lymphocytes,  36.5  percent. 
Eosinophiles,      1 
Many  of  the  lymphocytes  have  two  nuclei. 

No 

Diff    300     Polymorphonuclear   cells     41  7    per 

leucocy- 
tosis. 

cent. 
Lymphocytes,  48.4  per  cent. 
Eosinophiles,      9.3 
Myelocytes,          .6 

4 

-\I 

No 

Diff    500     Polymorphonuclear   cells,  60.2    per 

leucocy- 
tosis. 

cent. 
Lymphocytes,  36  percent. 
Eosinophiles,      5.6     ' 
Myelocytes,         2. 
Two  normoblasts. 

F 

Diff    500.     Polymorphonuclear   cells,    92.6   per 

cent. 
Lymphocytes,  5.2  per  cent. 
Myelocytes,       2.2 
No  eosinophiles. 

No 

Diff.  313.     Polymorphonuclear   cells,   62.3    per 

leucocy- 
tosis. 

cent. 
Lymphocytes,  37  per  cent. 
Myelocytes,      .6         " 

28 

M. 

5,218,000 

11,800 

85 

Polynuclear,              51  per  cent. 
Small  lymphocytes,  35 
Large 
Eosinophiles,               7 

HODGKIN'S   DISEASE. 
TABLE  X. — HODGKIN'S  DISEASE  (Continued). 


181 


Age. 

1 

Red 
cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

30 

M. 

5,280,000 

6,800 

55 

Diff.  Polymorphonuclear  cells,  76  per  cent. 
Lymphocytes,  22.3       " 
Eosinophiles,      1.4      " 
Myelocytes,           .3 
No  nucleated  red  cells. 

32 

M. 

4,616,000 

2,400 

70 

2,200 

Diff    Polymorphonuclear  cells,  69  per  cent. 

Small  lymphocytes,            19         " 
Large            "                       18 
Eosinophiles,                          4 
?ew  normoblasts. 

Wliite  Cells. 

When  inflammation  arises  in  the  glandular  tumors  and  some- 
times when  none  is  found,  the  white  cells  may  be  greatly  in- 
creased, even  up  to  a  ratio  of  1 :  80  red  cells,  as  in  Case  1  of  the 
present  series.  There  is,  however,  no  more  resemblance  to  leu- 
kaemia than  in  any  other  form  of  leucocytosis,  the  polymor- 
phonuclear  cells  alone  being  increased.  There  is  no  reason  for 
supposing,  as  Eeinert *  does,  that  relative  diminution  of  the 
lymphocytes  is  owing  to  the  diseased  condition  of  the  lymph 
glands,  for,  unless  oome  septic  process  gets  a  foothold  in  the 
glands,  the  lymphocytes  present  a  normal  number  or  even  (as 
in  Case  16)  considerably  increased  percentages.  Pfeiffer  2  has 
recently  reported  a  case  of  the  cutaneous  form  of  the  disease 
with  sixty  per  cent  of  lymphocytes  out  of  a  total  leucocyte  count 
of  6,500. 

As  in  any  other  cachectic  condition,  small  numbers  of  mye- 
locytes  may  be  found.  They  were  seen  in  six  of  our  cases  out 
of  eighteen  in  which  a  color  analysis  was  made,  the  highest  per- 
centage being  two  per  cent.  Eosinophiles  are  usually  decreased 
when  leucocytosis  is  present. 

Summary. 

Normal  blood  in  early  stages. 
Later  often  marked  anaemia. 
Sometimes  leucocytosis. 

1  "Die  Zahlung  der  Blutkorperchen, "  Berlin,  1891. 
2 Pfeiffer:  Wien.  klin.  Woch.,  1897. 


182 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


Diagnostic  Value. 

The  only  help  given  us  by  the  blood  is  in  excluding  leukae- 
mia. Syphilis,  tuberculosis,  or  malignant  disease  might  cause 
similar  blood  changes  or  lack  of  changes. 

EFFECTS  OF  SPLENECTOMY  ON  THE  BLOOD. 

Twenty-three  cases  are  on  record  in  which  the  blood  has 
been  studied  after  operation,  but  only  some  half-dozen  of  these 
are  carefully  recorded.  They  explain  themselves : 

TABLE  XL 


_c 

O       op 

•Si.  5 

1 

1 

1 

A 

j 

Red  cells. 

White 
cells. 

*! 

Polymorp 
nuclea 
neutrophi 

Small 
lymphocy 

Large 
lymphocy 

Eosinophil 

Averag 
diameter 
red  cell: 

Remarks. 

*1 

4,570,000 

8,000 

63 

Before  operation. 

4,  970,  000 

30,000 

64 

Three  days  after. 

5,  180,  000 

65,000 

77 

Six  days  after. 

4,  800,  000 

17,  500 

66 

Forty  -eight  days  after. 

4,  353,  000 

11,700 

85 

Four  months  after. 

3,  300,  000 

11,600 

85 

Five  years  after. 

•3 

3,200,000 

53,000 

65 



(  1893,  for  abscess.  )  Three 

weeks  after. 

4,500,000 

13,800 

80 

Four  months  after. 

t» 

1,634,000 

12,000 

45 

61 

16 

20 

3 

8.ij* 

Operated    (April  9th, 

1893)    for    malaria] 

hypertrophy    with 

twisted  pedicle.    April 

23d. 

2,460,000 

20,000 

87 

49 

18 

32 

1 

May  6th. 

4,530,000 

27,000 

110 

66 

18 

15 

1 

7.T> 

May  13th,  1894. 

3,977,000 

8,000 

100 

62 

21 

11 

6 

October  2d,  1895. 

f4 

4,850,000 

30,000 

108 

83 

8 

8 

1 

.... 

Operation    for  hypertro- 

p  h  i  e  d  ,       wandering 

spleen.     Before  opera- 

tion. 

4,700,000 

39,000 

100 

91 

5 

4 

0 

.... 

Seven  days  after. 

3,630,000 

18,000 

105 

78 

15 

6 

1 

.... 

Two  months  after. 

2,750,000 

20,000 

63 

84 

5 

10 

1 

Three  years  after. 

*Czerny :  Cited  in  Laudenbach ;  Arch,  de  Physiol.,  1896,  p.  724. 
f  Hartman  and  Vaquez :  Soc.  de  Biol.,  February  5th,  1895. 


PART  II. 

ACUTE  INFECTIOUS   DISEASES. 


CHAPTEE  in. 

INFLUENCE  OF  FEVER  ON  THE  BLOOD. 

SOME  of  the  blood-changes  found  in  acute  infections  are  to 
be  regarded  as  due  simply  to  the  fever  associated  with  the  dis- 
ease. It  is  worth  while,  therefore,  to  consider  what  fever  per  se 
can  do  to  the  blood. 

Maragliano '  and  others  have  shown  that  during  fever  from 
any  cause  a  contraction  of  the  peripheral  vessels  occurs.  When 
fever  disappears,  whether  spontaneously  or  from  the  action  of 
antipyretics  (phenacetin,  quinine,  etc.),  a  dilatation  of  the  ves- 
sels follows. 

Following  the  laws  to  which  we  have  so  often  alluded,  the 
contraction  of  the  vessels  causes  a  concentration  of  the  blood 
with  rise  in  specific  gravity  and  in  the  number  of  blood  cells  per 
cubic  millimetre.  This  concentration  is  still  further  increased 
by  the  greater  loss  of  water  which  the  organism  suffers  during 
fever  than  under  normal  conditions. 

The  effect  of  these  two  influences  in  increasing  the  number 
of  red  cells  per  cubic  millimetre  is,  however,  counteracted  to  a 
considerable  extent  by  the  sharing  of  the  blood  in  the  general 
tissue  destruction  which  goes  on  with  increased  rapidity  during 
fever.  Many  corpuscles  are  thus  destroyed,  but  until  the  tern- 
perature  falls  the  anaemia  is  covered  up  by  the  concentration. 
When  the  fever  leaves  the  patient  there  is  a  sharp  fall  in  the 
number  of  cells  per  cubic  millimetre,  due  partly  to  the  destruc- 
tion of  corpuscles  (hitherto  masked  by  concentration)  and  partly 
to  the  dilution  of  the  blood  which  is  the  result  of  the  post-febrile 
dilatation  of  the  peripheral  vessels  above  mentioned.  The  sud- 
1  Zeit.  f.  klin.  Med..  vols.  14  and  17. 


184  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

denness  of  this  fall  in  the  count  is  proportional  to  the  sudden- 
ness of  the  fall  in  temperature. 

The  alkalinity  of  the  blood  has  been  often  said  to  be  dimin- 
ished in  fever,  but  recent  research  tends  to  show  that  these  re- 
sults were  obtained  by  faulty  technique,  and  it  is  doubtful 
whether  the  reaction  of  the  blood  shows  any  constant  changes 
in  fever. 

Leucocytes  and  fibrin  show  no  constant  changes,  though  in 
the  majority  of  infectious  fevers  they  are  increased. 

PNEUMONIA. 
The  Blood  as  a  Whole. 

(a)  Bacteriology. — The  diplococcus  lanceolatus  has  been 
found  in  the  blood  of  pneumonic  patients  repeatedly,  especially 
in  those  in  whom  there  has  been  some  secondary  diplococcus 
infection  (e.g.,  diplococcus  endocarditis);  but  such  findings  are 
rare  and  have  generally  been  in  fatal  cases  with  very  severe  gen- 
eralized infection. 

For  example,  Sittmann  '  out  of  16  cases  found  diplococci  in 
the  blood  of  6,  most  of  which  were  complicated  with  lesions  in 
other  organs,  and  4  of  which  died,  while  of  the  10  whose  blood 
was  sterile,  9  recovered. 

Boulay 2  found  the  organism  in  2  cases  shortly  before  death. 
Belfanti 3  found  it  but  6  times  out  of  a  large  number  of  cases, 
and  ©f  these  6,  5  died.  Goldschneider 4  and  Grawitz 5  got  similar 
results.  Cohn6  in  32  cases  found  the  organism  in  9;  7  of 
these  died.  The  other  2  had  empyema  and  other  evidences 
of  metastatic  action  of  the  pneumococci.  Fraenkel  has  ob- 
tained over  300  colonies  from  one  puncture.  Their  virulence 
was  less  than  that  of  those  in  the  sputa,  showing  apparently 
the  effects  of  the  blood's  antitoxic  power.  Nevertheless,  it  is 
obvious  that  the  presence  of  pneumococci  in  the  blood  is  a  bad 
prognostic  sign. 

1  Deut.  Archiv  f.  klin.  Med.,  1894,  p.  323. 

2  Paris  Thesis,  1891. 

8  Riforma  Medica,  Naples,  1890,  No.  37. 
4Deut.  med.  Woch.,  1892,  No.  14. 
5Grawitz:  Charite-Annalen.  vol.  1«. 
6 Cohn:  Deut.  med.  Woch.,  1897,  No.  9. 


PNEUMONIA.  185 

(b)  Coagulation  is  remarkably  rapid  and  in  fresh  specimens 
the  fibrin  network  is  very  thick  and  appears  within  a  few 
minutes. 

(<?)  In  cases  with  cyanosis  the  blood  is  often  concentrated  at 
the  periphery  so  that  its  specific  gravity  is  high  and  the  number 
of  corpuscles  large. 

(d)  Monti  and  Berggriin '  observed  that  in  children  the 
specific  gravity  was  high  throughout  the  course  of  the  disease, 
falling  with  the  temperature. 

The  toxicity  of  the  blood  is  doubled  {Albu:  Yirchow's 
Archiv,  Yol.  149). 

Red  Cells. — During  the  fever  the  red  cells  are  approximately 
normal  (unless  increased  by  cyanosis) ;  but  after  the  crisis  there 
is  often  slight  anaemia,  due  partly  to  the  blood  destruction  evi- 
denced by  the  frequent  presence  of  hydrobilirubin  in  the  urine. 
Grawitz  considers  also  that  a  general  relaxation  of  the  peripheral 
vessels  in  the  post-critical  period  causes  a  dilution  of  the  blood 
with  (apparent)  lessening  of  the  red  cells. 

Maragliano  has  noticed  "degenerative"  changes  in  the  red 
cells  in  severe  cases,  but  as  a  rule  they  do  not  appear  much 
affected  either  in  quantity  or  quality  and  our  attention  is  chiefly 
directed  to  the 

White  Corpuscles. — 1.  Probably  as  early  as  the  time  of  the 
chill,  and  certainly  within  a  few  hours  after  it,  the  leucocytes 
are  greatly  increased,  and  continue  so  throughout  the  febrile 
period. 

2.  There  is  no  correspondence  between  the  daily  variations 
in  temperature  and  the  leucocyte  curve.      In  cases  in  which  a 
pseudo-crisis  occurs  (the  temperature  falling  but  quickly  rising 
again),  the  leucocyte  count  remains  high,  while  at  the  time  of 
the  true  crisis  and  often  a  few  hours  before  it  the  leucocytes  be- 
gin to  fall.     This  fall,  however,  is  hardly  ever  by  "crisis,"  but 
though  starting  perhaps  a  little  before  the  temperature  it  is  one 
to  two  days  longer  in  reaching  normal.     When  the  temperature 
reaches  normal  by  lysis  the  leucocytes  fall  with  it  but  generally 
more  slowly,  and  reach  normal  later. 

3.  When  resolution  is   delayed  the  leucocytosis  continues, 
sometimes  for  weeks,  and  very  gradually  sags  down  to  normal 
in  cases  in  which  resolution  eventually  occurs  without  complica- 


186  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

tion.     If  abscess,  empyema,  or  gangrene  follow,  the  leucocytes 
stay  up. 

4.  The  degree  of  leucocy tosis  is  probably  the  resultant  of 
the  factors  mentioned  on  page  106,  and  does  not  run  parallel  to 
the  degree  of  fever  or  the  amount  of  lung  involved.  Neverthe- 
less cases  with  extensive  signs  in  both  lungs  are  more  apt  to 
have  very  high  counts,  provided  the  "  reaction"  of  the  patient 
against  the  infection  is  vigorous.  The  cases  appear  to  fall 
into  the  following  groups  as  regards  the  degree  of  leucocytosis 
present. 

1.  Mild  infection,  vigorous  reaction  =  slight  leucocytosis. 

2.  Severe  or  moderate  infection,  vigorous  reaction  =  marked 

leucocytosis. 

3.  Severe  infection,  feeble  reaction  =  no  leucocytosis. 

(a)  The  cases  in  Class  1  all  recover,  but  they  are  very  few 
in  number,  (b)  Those  in  Class  2,  which  includes  over  nine- 
tenths  of  all  cases,  may  or  may  not  recover,  according  as  the 
fight  between  patient  and  disease  comes  out  one  way  or  the 
other. 

(c)  Class  3  almost  invariably  die ;  there  is  not  sufficient  of  a 
struggle  to  raise  the  leucocyte  count. 

Where  either  the  patient  or  his  disease  easily  gains  the 
mastery  there  is  no  leucocytosis  or  a  very  slight  one ;  but  in 
the  much  larger  class  of  cases  in  which  the  struggle  is  a  fierce 
one,  leucocytosis  appears,  whichever  way  the  struggle  results. 

Pick  '  noted  that  pneumonia  complicating  cases  of  small-pox 
which  were  already  very  sick,  caused  no  leucocytosis,  and  the 
same  is  often  true  in  those  whose  power  of  resistance  is  reduced 
by  age,  alcoholism,  typhoid,  or  by  some  chronic  disease. 

Von  Jaksch,  noticing  the  fatality  of  cases  without  leucocy- 
tosis, suggested  that  we  should  induce  leucocytosis  by  inject- 
ing turpentine  or  other  irritants  so  as  to  cause  abscess;  but 
this  has  not  proved  of  any  benefit  to  the  patient,  nor  has 
the  production  of  leucocytosis  without  abscess,  as  can  be 
done  with  pilocarpine  or  nuclein,  been  any  more  successful. 
There  is  no  difficulty  in  producing  the  leucocytosis  by  these 
means,  but  all  observers  are  agreed  that  it  does  the  patients 
no  good. 

Leucocytosis  is  checked  by  antipyretics  (Hare2)  but  not  by 

1  Arch.  f.  Dermat.  und  Syph.,  vol.  25,  p.  03. 

2  New  York  Medical  Record,  May  9th,  1896. 


PNEUMONIA. 


187 


cold  bathing,  which  speaks  in  favor  of  the  latter  method  of  re- 
ducing temperature. 

The  general  course  of  the  leucocytes  is  seen  in  the  accom- 
panying charts  from  Billings,  to  whose  excellent  article  I  am 
greatly  indebted. 


CHART  I.— PNEUMONIA,  SHOWING  FALL  BY  CRISIS  (BILLINGS). 

Feb.    |      16      |       17      I      18      I       19      I       20     I      SI      \       22      I 


705° 


102° 


99° 


98° 


60,000 


18,000 
6.000 

13,000 
J3.000 

woo 

s.ww 


4.000 
3,000 


The  upper  chart  shows  the  course  of  the  temperature,  the  lower  that  of 

the  leucocytes. 

Qualitative  Changes. — As  in  most  forms  of  leucocytosis  the 
polymorphonuelear  leucocytes  are  enormously  increased,  often 


188 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


making  over  ninety  per  cent  of  all  the  white  cells.  Eosinophiles 
and  blood  plates  disappear  and  the  lymphocytes  are  much  re- 
duced. After  the  crisis  this  is  reversed,  the  polymorphonuclear 
forms  falling  often  below  60  per  cent,  while  the  eosinophiles 
and  blood  plates  are  above  normal.  As  to  the  differential  count 


CHART  II.  —  PNEUMONIA  AND  RHEUMATISM. 


May. 


June. 


I 

( 

s 

L 

s 

7 

Si. 

P 

9 

3 

,7 

'• 

2 

3 

4 

£ 

106° 

/05° 

,*, 

104° 

/     \ 

103° 

102° 

\ 

i 

•* 

/0/° 

100° 

\ 

* 

^ 

99° 

• 

J 

^ 

93° 

•- 

- 

.V 

y 

* 

>^' 

... 

-I 

...v;. 

•V 

V 

«* 

97° 

80,000 

p 

.1 

. 

* 

c 

a 

V 

a 

n 

/ 

^ 

80,000 

/ 

\ 

*- 

-  «^ 

18,000 

f 

16,000 

j 

\ 

\ 

14,000 

?\ 

/ 

• 

12.000 

\ 

f 

\ 

V 

—  - 

10,000 

4 

/ 

8,000 

*• 

* 

6,000 

4,000 

3,000' 

The  upper  chart  shows  the  course  of  the  temperature,  the  lower  that  of 

the  leucocytes. 

in  the  (fatal)  cases  in  which  leucocytosis  is  absent,  data  are 
scanty.  Bieganski  thought  the  polymorphonuclear  varieties 
decreased,  Eieder  found  them  increased,  while  Billings  finds 
them  normal.  No  general  law  can  be  stated  on  this  point  as  yet. 
In  one  remarkable  case  occurring  at  the  Massachusetts 
General  Hospital  in  1894,  the  conditions  were  entirely  different 
from  those  just  stated.  The  patient,  a  girl  of  six,  had  at  en- 
trance 72,100  leucocytes  per  cubic  millimetre.  Two  days  after 


PNEUMONIA.  189 

the  count  was  94,600.  A  differential  count  made  at  the  same 
time  showed  that  the  small  lymphocytes  made  up  66  per  cent 
of  all  the  94,600  leucocytes  per  cubic  millimetre.  The  poly- 
morphonuclear  cells  were  reduced  to  30  per  cent.  Lymphatic 
leukaemia  was  thought  of,  but  the  leucocytosis  was  gone  in  ten 
days,  and  within  a  fortnight  the  patient  left  the  hospital  well. 
I  have  seen  one  reference  to  such  a  condition.  "  In  a  certain 
number  of  cases  the  leucocytosis  is  characterized  by  the  great 
number  of  the  youngest  forms  of  leucocytes.  This  condition 
persists  during  convalescence."1 

Diagnostic  and  Prognostic  Value. 

1.  In  cases  of  so-called  "central  pneumonia"  in  which  the 
symptoms  but  not  the  physical  signs  of  the  disease  are  manifest, 
the  presence  of  a  well-marked  leucocytosis  is  often  of  great  diag- 
nostic value.     It  excludes  malaria,  typhoid,  and  uncomplicated 
grippe  as  causes  of  fever,  and  if  scarlet  fever  and  suppuration 
can  be  excluded  by  other  evidence,  it  makes  pneumonia  very 
probable. 

I  have  repeatedly  seen  the  diagnosis  of  pneumonia  made  in 
the  absence  of  physical  signs  and  largely  on  the  evidence  of  the 
blood  count,  the  diagnosis  being  confirmed  several  days  later  by 
the  appearance  of  typical  signs  of  consolidation.  In  a  case  of 
Dr.  F.  C.  Shattuck's,  sick  five  days,  yet  showing  no  signs  of 
consolidation  of  the  lung,  the  presence  of  a  marked  leucocytosis 
excluded  typhoid,  the  only  other  likely  diagnosis,  and  led  Dr. 
Shattuck  to  treat  the  case  as  pneumonia,  the  wisdom  of  which 
course  was  later  demonstrated  by  the  appearance  of  signs  of 
consolidation. 

2.  Between  pneumonia  and  capillary  bronchitis  the  condition 
of  the  blood  is  of  no  help,  as  the  latter  also  causes  leucocytosis, 
and  some  cases  affecting  the  larger  tubes  do  the  same. 

3.  In   cases  of    pneumonia  occurring  in  very   old  or   very 
3roung  people,  in  which  the  fever  and  symptoms  may  be  very 
slight,  the  presence  of  leucocytosis  may  be  the  first  thing  to 
direct  our  attention  to  the  lungs,  dyspnoaa  and  cough  being  ab- 
sent. 

'Stienon:  Jour,  de  Med.,  de  Chirurg.  et  de  Pharm.,  Bruxelles,  1895, 
t.  iv.,  fasc.  1. 


190 


SPECIAL   PATHOLOGY   OF   THE  BLOOD. 


In  prognosis,  the  important  point  is  that  the  absence  of  leu- 
cocytosis  is  a  very  bad  sign,  ivhile  its  presence  is  neither  good 
nor  bad.  It  must  be  remembered  also  that  in  the  very  mildest 
cases  we  may  find  the  same  absence  of  leucocytosis  which  in 
any  other  but  the  mildest  would  be  almost  surety  fatal. 

This  last  point,  which  appears  to  rne  of  great  importance,  is 
illustrated  by  the  following  figures  : 

Halla  reported  14  cases  ;  2  had  no  leucocytosis,  and  both  died. 

Billings  reported  22  cases  ;  1  had  no  leucocytosis  and  died. 

Laehr  with  16  cases,  and  Bieder  with  26,  got  similar  results. 

Ewing  in  101  cases  found  leucocytosis  absent  in  6  ;  6  died. 

Yon  Jaksch  and  Kilodse  likewise  maintain  that  the  absence 
of  leucocytosis  is  usually  fatal. 

In  the  Massachusetts  General  Hospital  329  cases  have  been 
studied.  In  general  they  entirely  confirm  the  results  obtained 
by  Billings  and  summarized  above;  32  of  them  presented  no 
leucocytosis  at  any  time,  and  of  these  32,  30  died,  another  one 
seemed  moribund  but  finally  recovered,  while  the  remaining 
case  was  a  very  mild  one. 

The  evidence,  therefore,  is  overwhelmingly  in  favor  of  the 
view  that  where  leucocytosis  is  absent  in  any  but  the  mildest 
cases  the  prognosis  is  almost  fatal.  The  presence  of  leucocyto- 
sis, on  the  other  hand,  is  no  guaranty  whatever  of  a  favorable 
issue. 

The  series  of  cases  at  the  Massachusetts  Hospital  is  too  large 
to  exhibit  in  tabular  form.  Their  results  may  be  summarized 
as  follows  : 

Cases  with  leucocytes  under  10,000  =  32  (30  of  these  fatal) 
between  10,000  to  15.000  =  38 
15,000  "  20,000  =  72 
20,000  "  25,000  =  65 
25,000  "  30,000  =  37 
30,000 
35,000 
40,000 
45,000 


50,000 


35,000  =  22 
40,000=  4 
45,000=  7 
50,000=  4 
55,000=  5 


but  not  accurately  counted  =  43 


Average  =  24, 000  - 


329 


TYPHOID    FEVER.  191 

TYPHOID   FEVER. 
Bacteriology, 

Although  the  bacilli  of  Eberth  are  occasionally  to  be  found 
in  the  blood  by  culture,  it  is  only  in  the  marked  cases  that  they 
occur,  and  then  but  rarely,  so  that  at  present  we  derive  no  help 
in  doubtful  cases  by  the  bacteriological  examination  of  the  blood. 

Kiihnau,  using  5-10  c.c.  of  blood,  found  the  organism  in  10 
out  of  41  cases,  from  2  to  9  slow-growing  colonies  in  each. 
Other  observers  have  been  successful  in  only  7  out  of  a 
total  of  176  cases  examined.  Block  has  recently  succeeded  in 
isolating  the  organism  twice  during  the  life  of  a  patient  who  sub 
sequently  died.  In  6  other  cases  he  was  unsuccessful.  It  has 
been  asserted  that  when  the  bacilli  enter  the  blood  the  serum 
reaction  (vide  infra)  does  not  appear. 

Toward  the  end  of  th-  disease,  when  the  temperature  is  apt 
to  be  very  irregular  (so-called  "  period  of  steep  curves"),  pyogenic 
cocci  are  occasionally  to  be  found  in  cultures  made  from  the 
blood,  and  doubtless  account  for  many  of  the  recrudescences  and 
temporary  febrile  attacks,  with  or  without  chills,  which  are  so 
common  in  early  convalescence. 

The  Blood  as  a  Whole. — 1.  Coagulation  and  fibrin  are 
normal. 

2.  Specific  gravity  follows  the  course  of  the  haemoglobin. 

3.  The  general  effects  of  fever  (see  above,  page  183)  are  in 
part  accountable  for  the  changes  next  to  be  described,  while 
some  of  them  are  more  peculiar  to  typhoid  fever. 

Red  Cells. — During  the  first  two  weeks  there  are  no  consid- 
erable changes,  except  in  so  far  as  a  certain  amount  of  concen- 
tration of  the  blood  with  apparent  increase  of  cells  may  be 
brought  about  by  diarrhoea  or  sweating.  Baths  have  a  like 
effect  if  the  blood  is  examined  just  after  the  immersion. 1  In 
the  third  week  the  red  cells  usually  begin  to  decrease  and  in  ex- 
treme cases  may  get  as  low  as  1,300,000  at  the  beginning  of  con- 
valescence— i.e.,  when  body  weight  begins  to  increase.  Hay  em 
considers  that  the  diminution  begins  rather  suddenly  in  the 
middle  or  end  of  the  third  week  of  severe  cases,  but  according 

1  Antipyrin  and  acetanilid  have  no  effects  on  the  red  cells. 


192  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

to  Thayer  the  diminution  is  gradual,  though  at  first  sight,  grow- 
ing more  rapid  at  the  time  of  defervescence,  and  continuing 
often  into  convalescence.  The  lowest  point  is  reached  about  the 
first  week  of  convalescence. 

The  following  figures  (Thayer)  illustrate  this. 

First  week,       Second  week,       Third  week,       Fourth  week,      Fifth  week,        Sixth  week. 
2  counts.  10  counts.  9  counts.  6  counts.  7  counts. 

5,636,000        4,960,599        4,951,535        4,038,333        3,856,786        4,364,250 

His  later  counts  show  a  gradual  increase.  He  finds  that  the 
amount  of  anaemia  bears,  as  a  mde,  a  direct  relation  to  the 
severity  of  the  case,  but  in  one  of  his  cases  a  grave  anaemia 
(1,300,000)  followed  a  mild  attack.  "  The  anaemia  may  be  severe 
enough  to  form  of  itself  a  dangerous  complication  of  the  proc- 
ess." Henry  has  likewise  recorded  counts  as  low  as  1,306,000 
and  804,000  in  two  convalescent  typhoids. 

Hcemoglobin. — The  loss  of  coloring  matter  roughly  parallels 
that  of  the  red  cells,  but  is  always  relatively  greater  and  is 
slower  in  reaching  normal.  In  the  case  just  noted  it  was  20  per 
cent,  color  index  .7. 

Leucocytes. — The  absence  of  anv  increase  oi  the  white  cells 
is  the  most  important  point. 

Starting  with  an  approximately  normal  count,  the  number 
falls  during  the  fever,  often  below  2,000,  according  to  Hay  em, 
and  sometimes  below  1,000  per  cubic  millimetre.  Khetagurow 
finds  the  lowest  counts  (2,500-3,000)  about  the  end  of  the  third 
week. 

Thayer 's  figures  are  as  follows : 

First  week,       Second  week,     Third  week,     Fourth  week.    Fifth  week,     Sixth  week, 
21  counts.  50  counts.          40  counts.          28  counts.         16  counts.  5  counts. 

6,984  6,468  6,260  5,877  6.621  7,000 

In  the  four  hundred  and  ninety-one  cases  counted  at  the 
Massachusetts  General  Hospital,  the  course  of  the  leucocytes 
has  unfortunately  not  been  followed  by  weeks  with  sufficient 
accuracy  to  make  comparisons  of  value.  In  a  general  way, 
however,  they  corroborate  all  of  Thayer's  positions.  At  the  be- 
ginning of  the  cases  the  count  was  often  high  (11,000),  owing 
probably  to  concentration  of  the  blood  by  starvation  and  diar- 
rhoea. The  high  count  of  red  cells  confirmed  this,  the  ratio  of 
red  to  white  remaining  normal.  The  counts  of  leucocytes  then 
gradually  diminished,  as  in  Thayer's  cases. 


TYPHOID    FEVER.  193 

The  range  of  the  counts  was  as  follows : 

Between    1,000  and    2,000=  7  cases. 

2,000    "       3,000=  33  " 

3,000    "      4,000=  59  " 

4,000    "       5,000=  108  " 

5,000    "      6,000=  82  " 

6,000    "       7,000=  72  " 

7,000    "       8,000=  47  " 

8,000    "      9,000=  37  " 

9,000    "     10,000=  29  " 

10,000    "     11,000=  10  " 

Over         11,000 =  7  " 

491  cases. 

From  these  figures  I  have  excluded  all  cases  counted  only 
under  circumstances  likely  to  concentrate"  the  blood  (cyanosis, 
after  baths,  after  severe  diarrhoea). 

There  is  no  doubt  that  leucocytosis  does  occasionally  occur 
when  no  complication  exists  so  far  as  loe  can  ascertain  during 
life.  Four  of  the  cases  over  11,000  (see  the  above  table)  were 
counted  repeatedly  and  complications  were  carefully  sought  for, 
but  none  were  found.  The  most  striking  case  showed  the  fol- 
lowing counts : 

October    3d 13,100 

4th 13,000 

5th 16,500 

7th 13,300 

8th 11,200 

"        10th 10,600 

13th 13,500 

15th 17,700 

17th 15,500,  death  ;  autopsy. 

The  autopsy  showed  typical  typhoid  lesions  and  nothing 
else.1  Another  and  much  milder  case  showed  11,000-12,000 
white  cells  constantly  for  over  two  \v^eks,  and  no  cause  could  be 
found  to  account  for  it. 

The  great  rarity  of  such  cases  and  constant  association  of 
leucocytosis  with  any  of  the  numerous  complications  which  we 
can  recognize,  rather  inclines  me  to  the  belief  that  in  all  the 
cases  in  which  leucocytosis  exists  constantly,  some  complication 

1  Thrombosis  of  internal  veins  and  osteomyelitis  were  not  carefully 
searched  for  at  autopsy  and  may  have  existed. 
13 


194  SPECIAL,   PATHOLOGY   OF   THE   BLOOD. 

really   is  present  though  unrecognized.      The  possibility  of  a 
secondary  septic  infection,  of  an  osteomyelitis,  or  phlebitis  of 
internal  veins  cannot  be  excluded  without  further  evidence. 
Examples  of  the  effect  of  complications  are  as  follows: 
Perforation. — Case  I.    (a)  Five  days  before  perforation,     8,300 
(b)  At  time  of  the  perforation,  .    24,000 
Case  II.       At  time  of  perforation,     .     .     18,500 
Phlebitis. — Case  I.   (a)  Two  days  before  onset,  .     .       6,400 

(b)  At  time  of  the  onset,  .     .     .     12,900 

(c)  One  week  later,       ....     10,100 
Case  II.   (a)  One  week  before  onset,    .     .      4,800 

(b)  At  time  of  onset,    ....    16,200 

Otitis  Media. — Case  I.  (a)  At  entrance, 5,300 

(6)  Mastoid  abscess,    ....    16,400 

Case  II.  (a)  At  entrance, 8,400 

(b)  Two  weeks  later,  after  open- 
ing drum  membrane 
(sero-pu  rulent  clis- 

charge), 11,200 

Case  III.   (a)  At  entrance, 7,320 

(b)  Otitis, 14,000 

A  freely  discharging  otitis  soon  ceases  to  cause  leucocytosis, 
e.g.,  a  case  of  serous  otitis  media  seven  days  after  puncture, 
but  still  freely  discharged,  showed  but  5,320  white  cells  per 
cubic  millimetre. 

An  abscess  of  the  buttock  raised  the  count  from  8,000  to 
11,200,  and  a  hemorrhage  from  8,000  to  11,300. 

General  bronchitis  has  usually  no  effect  in  augmenting  the 
leucocyte  count  unless  the  disease  invades  the  smallest  tubes 
(capillary  bronchitis).     Thus  two  cases  of  this  affection  showed 
9,000  and  8,000  leucocytes  respectively. 
Cystitis  had  no  effect  in  two  cases.1 

In  two  cases  whose  symptoms  simulated  otitis  (deafness, 
rise  of  temperature,  pain  in  the  head,  and  in  one  a  convulsion) 
but  whose  blood  counts  were  normal,  the  trouble  turned  out  to 
l>e  functional  and  nothing  came  of  it,  the  symptoms  disappear- 
ing within  twenty -four  hours. 

1 1  have  an  impression  based  on  rather  fragmentary  evidence  that  com- 
plications directly  due  to  the  Eberth  bacilli,  e.g.,  Eberth  cystitis  or  Eberth 
pneumonia,  do  not  raise  the  leucocyte  count.  I  hope  to  investigate  this 
point  later. 


TYPHOID    FEVER.  195 

Some  observers  l  have  noted  a  slight  leucocytosis  at  the  be- 
ginning of  convalescence.  Thayer  did  not  find  this,  and  I  have 
been  equally  unsuccessful. 

It  occasionally  happens  in  very  exhausted  patients  that  com- 
plications fail  to  produce  any  leucocytosis,  the  patient  (as  in 
some  fatal  cases  of  pneumonia  or  purulent  peritonitis)  being 
unable  to  react  against  the  infection.  For  example,  I  have  seen 
a  large  ischio-rectal  abscess  develop  in  a  moribund  typhoid 
patient  without  producing  any  effect  on  the  leucocyte  count. 
Von  Limbeck  has  noticed  the  same  lack  of  reaction  in  typhoid 
patients  after  a  hemorrhage  and  bronchopneumonia,  and  Eieder 
in  croupous  pneumonia  occurring  as  a  complication. 

These  cases,  however,  are  exceptional,  and  in  many  of  them 
the  percentage  of  adult  leucocytes  rises,  though  no  increase  in 
the  total  leucocyte  count  is  present.  This  increased  percentage 
of  polymorphonuclear  forms  generally  betrays  the  presence  of 
the  complication,  since  during  most  of  the  disease  (if  uncompli- 
cated) the  polymorphonuclear  forms  are  diminished. 

In  normal  cases  the  blood  begins  to  return  to  normal  as 
soon  as  the  fever  is  gone  and  reaches  the  normal  in  the  sixth  or 
seventh  week. 

Qualitative  Changes. 

Red  Cells. — The  condition  is  either  normal  or  shows  the 
changes  common  to  all  varieties  of  secondary  ansemia. 

White  Cells. — All  observers  are  agreed  upon  the  following 
changes : 

1.  The  polymorphonuclear  cells  progressively  diminish  with 
a  corresponding  increase  in  the  lymphocytes.     This  change  is 
but  slight  in  the  first  two  weeks,  but  grows  marked  in  the  latter 
part  of  the  illness,  the  polymorphonuclear  cells  falling  below 
50  per  cent.     Among  the  lymphocytes,   the  larger  forms  pre- 
dominate. 

2.  It  is  not  until  after  the  disappearance  of  fever  (from  three 
to  ten  days  after  it,  according  to  Ouskow)  that  the  polymorpho- 
nuclear cells  begin  to  increase  again  and  their  normal  percentage 

1  E.g.,  Aporti  and  Radaeli  (llth  Congress  for  Medical  Science,  Rome, 
March  29th,  1894) . 


196  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

is  not  reached  until   the  tenth   or   eleventh   week.     Thayer's 
differential  counts  show : 

Second  week,          Third  week,  Fourth  week,  Fifth  week.  Sixth  week, 

5  counts.  1  count.  3  counts.  1  count.  2  counts. 

71. 7  per  cent.     66. 5  per  cent.     65. 3  per  cent.     58. 5  per  cent.     53. 4  per  cent. 
3.  Eosinophiles  are  present  in  small  numbers. 

Summary. 

1.  Post-febrile  anaemia,  sometimes  very  intense. 

2.  No  leucocy tosis ;  in  late  weeks  leucopenia. 

3.  Increased  percentage  of  lymphocytes  at  the  expense  of 
polymorphonuclear  forms,  especially  marked  in  later  weeks. 

4.  Most  complications  cause  leucocy  tosis. 

Diagnostic  Value. 

There  are  few  diseases  (outside  of  those  known  as  diseases 
of  the  blood  itself)  in  which  the  blood  count  is  so  often  of  value  in 
diagnosis.  The  diagnosis  of  typhoid  fever  is  to  be  made  by  ex- 
clusion— exclusion  of  other  causes  of  fever  and  of  local  inflam- 
matory processes  in  particular. 

1.  Now  in  this  process  of  exclusion,  the  blood  is  a  most 
powerful  adjuvant,  inasmuch  as  almost  all  local  inflammatory 
processes  have  leucocytosis,  while  typhoid  (uncomplicated)  does  not. 
I  have  seen  two  cases  in  which  the  chart  and  symptoms  pointed 
to  typhoid  but  in  which  the  persistent  marked  leucocytosis 
directed  attention  to  the  search  for  an  inflammatory  focus.     Both 
were  at  first  unattended  with  pain,  tenderness,  or  other  localiz- 
ing symptom,  but  later  signs  and  symptoms  began  to  point  to 
the  liver,  from  which  pus  was  evacuated  by  puncture.     These 
cases  of  abscess  of  the  liver  are  typical  of  the  value  of  blood  ex- 
amination for  any  deep-seated  suppuration.     I  have  seen  good 
clinicians  puzzled  for  twenty -four  hours  over  the  diagnosis  be- 
tween appendicitis  and  typhoid,  but  the  indication  of  the  blood 
count  was  always  fulfilled.     All  pyaemic  or  septicsemic  processes 
are  distinguishable  from  typhoid  by  the  same  test — the  pres- 
ence of  leucocytosis  in  the  former. 

Of  the  value  of  the  blood  in  distinguishing  certain  cases  of 
pneumonia  from  typhoid  I  have  already  spoken  on  page  189. 

2.  Aside  from  local  or  general  pyogenic  infections  perhaps 
the  disease  most  often  confounded  with  typhoid  is  malaria. 


TYPHOID   FEVER.  197 

This  is  especially  the  case  in  the  southern  part  of  this  country, 
where  for  want  of  proper  blood  examination  the  confusion  of  the 
two  diseases  is  indicated  in  such  a  term  as  "  typho-malarial 
fever."  Malaria  and  typhoid  are  alike  in  having  no  leucocy- 
tosis,  but  the  presence  of  the  malarial  parasite  is  an  absolute 
test  and  in  marked  cases  is  always  decisive.  Very  mild  cases 
of  malaria  may  show  so  few  organisms  in  the  peripheral  circu- 
lation that  without  prolonged  search  they  cannot  be  found,  and 
in  the  severest  types  of  all,  the  organisms  are  not  very  abun- 
dant. In  the  vast  majority  of  cases,  however,  the  organism  can 
be  readily  found  and  our  diagnosis  made  certain. 

3.  Tuberculosis,  if  uncomplicated  by  any  pyogenic  organ- 
isms, cannot  be  distinguished  from  typhoid  by  the  examination 
of  the  blood  alone,  as  neither  disease  shows  leucocytosis. 

A  large  proportion  of  lymphocytes  is  commoner  in  typhoid 
than  in  tuberculosis,  but  it  may  occur  in  either  disease.  In  the 
majority  of  cases,  however,  tuberculosis  is  complicated  with 
septicaemia  from  a  secondary  pyogenic  infection,  and  is  then 
easily  distinguished  by  the  existence  of  leucocytosis. 

4.  Typhus  fever  has  not  been  well  studied  and  the  reports  of 
its  blood   condition  are  contradictory.     At  present  we  cannot 
say  whether  or  not  it  can  be  distinguished  from  typhoid  by  the 
blood  examination.     In  most  cases  the  absence  of  a  serum  reac- 
tion will  exclude  typhus. 

5.  Two  cases  of  erythema  nodosum  with  fever  between  101° 
and  103°  gave  me  trouble  in  diagnosis  lately.     In  both  the  blood 
was  normal  and  differed  from  typhoid  only  by  the  absence  of  a 
serum-reaction. 

The  occurrence  of  complications  in  typhoid  may  mask  its 
characteristic  blood  changes  so  as  to  make  the  blood  useless  in 
diagnosis ;  but  in  most  early  cases,  in  which  the  diagnosis  is  es- 
pecially important  and  difficult,  the  blood  shows  no  leucocytosis 
and  is  therefore  of  great  value  in  the  exclusion  of  other  diseases. 

DIPHTHERIA. 

Bacilli  of  diphtheria  in  the  circulating  blood  are  practically 
never  to  be  found. 

The  specific  gravity,  according  to  Grawitz,  is  above  normal  at 
the  height  of  the  disease.  He  obtained  the  same  result  experi- 


198  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

mentally  by  injecting  cultures  of  the  Klebs-Loffler  bacillus 
into  dogs  and  rabbits.  He  concludes  that  the  poison  of  the 
disease  is  lymphagogic  and  so  concentrates  the  blood. 

Red  Corpuscles. — Morse's  1  investigations  show  an  average  of 
5,100,000  in  twenty  cases  counted  during  the  first  week  of  the 
disease  and  of  5,150,000  in  10  cases  during  the  second  and  third 
week  of  the  disease — practical^  normal  figures. 

These  are  the  first  systematic 2  investigations  of  the  red  cells 
in  diphtheria  and  are  confirmed  by  the  reports  of  Ewing,  Engel, 
and  Billings.  The  latter  observer  in  counts  made  in  seven  cases 
during  the  first  five  days  of  illness  found  an  average  of  5,600,- 
000-h  red  cells  per  cubic  millimetre.  During  the  first  five  to  ten 
days  after  this,  the  same  cases  showed  an  average  loss  of  510,000 
cells  per  cubic  millimetre ;  five  out  of  the  seven  showing  consid- 
erable losses,  two  remaining  about  the  same.  These  were  cases 
treated  without  antitoxin.  The  two  cases  showing  no  loss  of 
red  cells  were  both  very  mild,  one  having  no  membrane  at  any 
time.  The  diminution  ranged  from  470,000  (third  day)  to 
2,040,000  (sixth  day).  As  a  rule  no  diminution  can  be  made 
out  until  after  the  third  or  fourth  day. 

Out  of  twenty-three  cases  treated  with  antitoxin  and  each 
counted  several  times  over,  only  three  showed  any  considerable 
diminution  in  the  red  cells  and  these  lost  less  than  400,000 
each,  not  much  beyond  the  limit  of  error  (200,000)  allowed  for 
by  the  investigator,  and  all  of  them  severe  cases.  Six  patients 
who  were  anaemic  when  admitted  (average =4, 640, 000)  showed  a 
steady  rise  in  the  red  cells  as  the  disease  (treated  with  anti- 
toxin) progressed. 

It  is  evident  from  these  figures  that  antitoxin  largely  pre- 
vents the  anaemia  which  usually  develops  in  the  first  five  to  ten 
days.  In  cases  not  treated  with  antitoxin  the  regeneration 
from  the  resulting  anaemia  is  slow.  Healthy  individuals  in- 
jected with  antitoxin  showed  a  very  moderate  reduction  in  the 
red  cells  in  about  one-half  the  cases,  the  greatest  loss  being  932,- 
000  per  cubic  millimetre  (fifteen  cases  counted  by  Billings) . 

Qualitative  CJianges. — Billings'  careful  study  of  stained  speci- 
mens showed  no  deformities  in  size  or  shape  and  no  nucleated 
red  cells.  Polychromatophilic  red  corpuscles  were  very  few  in 

1  Boston  Medical  and  Surgical  Journal,  March  7th,  1895. 

2  Earlier  reports  are  faulty  as  to  technique. 


DIPHTHERIA.  199 

the  cases  in  which  antitoxin  was  used,  but  more  numerous  where 
it  was  not  used. 

Haemoglobin. — Here  again  the  most  thorough  investigations 
are  those  of  Billings.  In  cases  treated  without  antitoxin  there 
was  an  average  loss  of  ten  per  cent,  regained  in  part  during  con- 
valescence, but  as  usual  reaching  normal  later  than  the  count 
of  corpuscles.  When  antitoxin  was  given,  the  diminution  of 
haemoglobin  was  less  marked,  but  where  the  decrease  did  occur 
the  return  to  normal  was  slow  compared  to  that  of  the  red  cells, 
even  when  the  patients  were  up  and  about  and  apparently  well. 

White  Corpuscles. — Leaving  out  the  older  observations  in 
which  the  technique  was  probably  faulty,  the  principal  investi- 
gators are  Morse,  Ewing,  Gabritschewsky,  and  Billings. 

All  agree  that  a  considerable  leucocytosis  is  present  in  most 
cases— 34  out  of  36  of  Billings'  cases,  26  out  of  30  of  Morse's  (the 
latter  made  but  one  count  in  each  case),  49  out  of  53  of  Ewing' s. 
In  a  general  way,  the  severest  cases  show  the  greatest  leucocy- 
tosis, but  it  does  not  follow  the  pulse,  temperature,  nor  the  ex- 
tent of  the  membrane,  and  "  the  ordinary  clinical  examination 
of  the  patient  is  of  much  greater  value  in  ...  prognosis  .  .  . 
than  any  information  to  be  gained  from  the  examination  of  the 
blood.  The  latter  is  simply  confirmatory,  never  indispensable" 
(Billings).  Morse's  conclusions  are  the  same,  although  he  con- 
siders that  with  notable  exceptions  the  amount  of  membrane  is 
a  rough  measure  of  the  degree  of  leucocytosis.  He  finds  no 
correspondence  between  the  glandular  swellings  and  the  degree 
of  leucocytosis,  though  he  noted  that  "  in  the  fatal  ' septic'  cases 
with  greatly  enlarged  glands, "  very  high  counts  were  present. 
Other  cases  with  little  or  no  enlargement  of  glands  showed 
equally  high  counts,  however. 

Swing's  4  cases  without  leucocytosis  were  all  mild,  but  of 
Billings'  2  cases  without  leucocytosis  one  was  the  severest  of 
his  whole  series,  while  the  other  was  rnild.  Of  Morse's  4  cases 
without  leucocytosis  3  were  mild  and  1  severe.  Gabritschew- 
sky's  14  cases  all  showed  leucocytosis. 

Putting  the  results  of  these  four  observers  together  we  see 
that  when  leucocytosis  is  absent  the  cases  are  either  very  mild 
or  very  severe,  conditions  analogous  to  those  to  be  noted  in  pneu- 
monia and  septicaemia.  The  counts  in  recent  epidemics  range 
from  normal  to  48,000  (Morse)  or  to  38,600  (Billings).  Felsen- 


200  SPECIAL    PATHOLOGY   OF   THE   BLOOD. 

thai l  found  148,229  per  cubic   millimetre    in    one    case,    and 
Bouchut's 2  counts  are  often  over  75,000. 

In  a  general  way  the  counts  rise  while  the  disease  progresses 
and  fall  gradually  as  improvement  goes  on,  disappearing  after 
the  membrane.  "  The  leucocy tosis  is  well  marked  by  the  third 
day  and  very  likely  earlier"  (Morse).  Billings  found  an  in- 
crease after  one  day's  illness,  but  usually  less  than  was  present 
later  in  the  disease ;  one  of  his  cases,  however,  had  a  higher  count 
on  the  first  day  of  the  disease  than  on  any  subsequent  day, 
though  no  antitoxin  was  given. 

The  injection  of  antitoxin  has  apparently  no  effect  upon 
the  leucocyte  count  (strange  to  say)  except  in  the  first  twenty- 
four  hours  after  its  use.  Immediately,  i.e.,  within  thirty  min- 
utes after  an  injection,  the  leucocytes  are  stated  by  Ewing 
to  be  considerably  diminished,  but  the  leucocyte  curve  does 
not  reach  normal  any  sooner  than  in  cases  in  which  no  anti- 
toxin is  given,  although  it  begins  to  fall  in  the  majority  of  cases 
after  the  injection.  The  same  thing  (according  to  Billings) 
takes  place  without  antitoxin. 

The  leucocytes  of  healthy  persons  are  likewise  unaffected 
by  antitoxin  injections. 

Qualitative  Changes. — All  authors  agree  that  in  most  cases 
the  neutrophiles  are  increased.  Morse  found  an  average  of  80 
per  cent  in  26  of  his  30  cases.  Of  the  other  4,  1  was  normal 
and  3  subnormal  (58,  59,  and  59  per  cent) ;  2  of  these  were  con- 
valescent, the  other  had  been  sick  a  week  and  had  12,000  white 
cells  per  cubic  millimetre.  A  similar  lymphocytosis  was  present 
in  1  of  Ewing' s  53  cases,  and  in  1  of  Eieder's  during  convales- 
cence. Billings  thinks  such  a  lymphocytosis  may  be  present 
in  perfect  health,  mentioning  cases  with  32,  33,  and  35  per  cent 
of  small  lymphocytes  in  sound  persons.  Such  a  condition  did 
not  occur  in  any  of  his  diphtheritic  cases  except  in  the  single 
fatal  case  without  leucocytosis.  Here  the  polymorphonuclear 
cells  were  reduced  to  55  per  cent  and  the  lymphocytes  (large 
and  small)  made  up  the  remaining  45  per  cent,  28  per  cent  being 
large  forms.3  In  the  rest  of  his  cases  the  polymorphonuclear 

1  Archiv  f.  Kinderheilk. ,  vol.  xv.,  p.  78,  1893. 

2  Comptes  Kendus,  1877,  Ixxv. ,  No.  3. 

3 In  Rieder's  case  above  referred  to,  aged  three  years,  the  lymphocytes 
rose  from  19  per  cent  during  the  fever  to  64  per  cent  in  convalescence. 


DIPHTHERIA.  201 

varieties  averaged  80  per  cent  and  the  lymphocytes  19  per  cent, 
the  eosinophiles  being  reduced  to  1  per  cent  on  the  average  and 
often  being  entirely  absent.  With  Morse  eosinophiles  averaged 
2  per  cent. 

The  proportion  of  polymorphonuclear  cells  is  usually  directly 
proportional  to  the  total  increase  of  leucocytes. 

Ewing  thinks  that  "  the  staining  reaction  of  the  leucocytes  is 
an  accurate  measure  of  the  severity  of  the  diphtheritic  infection," 
and  this  staining  reaction  he  finds  increased  in  favorable  cases 
by  the  injection  of  antitoxin. 

Billings  did  not  find  any  such  changes  in  "  staining  reaction," 
though  he  claims  to  have  carefully  followed  out  Ewing' s  pro- 
cedures. 

Engel1  found  that  antitoxin  at  first  slightly  increased  the 
percentage  of  lymphocytes,  and  sometimes  this  increase  was  very 
marked.  In  one  case  the  lymphocytes  increased  from  24  to  65 
sixty-five  per  cent  after  antitoxin. 

The  point  on  which  he  specially  insists  is  the  presence  of 
considerable  numbers  of  myelocytes  in  fatal  cases. 

Of  the  cases  examined  by  him  17  died,  and  9  of  these  had 
from  3.6  to  16.8  per  cent  of  myelocytes  in  every  one  hundred 
leucocytes.  Myelocytes  were  also  present  in  some  of  the  cases 
which  recovered,  but  in  smaller  numbers  (1.3  to  1.5  per  cent.) 

In  one  case  he  found  on  the  third  day  of  the  disease  4.3  per 
cent  of  myelocytes,  and  from  this  point  the  percentage  gradually 
rose  to  13.8  per  cent,  and  then  fell,  there  being  1.7  per  cent 
present  at  the  time  of  death.  An  abscess  occurring  in  the  case 
showed  only  the  usual  polymorphonuclear  leucocytes  in  its  con- 
tents. He  concluded  that  a  large  percentage  of  myelocytes  is  a 
bad  prognostic  sign  in  any  case. 

Myelocytes  are  not  mentioned  in  any  of  the  numerous  differ- 
ential counts  made  by  Gabritschewsky,  Ewing,  Morse,  and  Bill- 
ings, so  that  Engel' s  observation  is  so  far  unique. 

Summary. 

1.  Moderate  anaemia,  especially  in  cases  treated  without  an- 
titoxin.    Regeneration  is  slow. 

2.  Leucocytosis,  very  roughly  parallel  to  the  severity  of  the 
disease,  unaffected  by  antitoxin  treatment,  gradually  decreas- 

1  Gesellsch.  f .  innere  Med. ,  Berlin,  July  6th,  1896. 


202  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

ing  the  disease  passes  off,  sometimes  absent  in  very  mild  or 
very  severe  cases. 

3.  Polymorphonuclear  leucocytes  much  increased  during  fe- 
brile stages,  often  diminished  in  convalescence. 

4.  Myelocytes  numerous  in  some  severe  cases. 

The  blood  examination  has  no  diagnostic  value  so  far  as  I 
can  see ;  in  prognosis  the  absence  of  leucocytosis  (except  in  ob- 
viously mild  cases)  and  the  presence  of  many  myelocytes  are  ap- 
parently bad  signs. 


CHAPTEE  IV. 

ACUTE  INFECTIOUS  DISEASES   (CONTINUED). 
SCARLET    FEVER. 

HEUBNEB*  noted  hsemoglobinsemia  in  one  case.  Fibrin  is 
not  increased  even  at  the  height  of  the  fever,  provided  inflam- 
matory complications  are  absent. 

Red  Cells. — Very  little  is  to  be  found  in  literature  upon  the 
subject.  Kotschetkoff 2  noted  a  gradual  diminution  of  the  red 
cells  to  about  3,000,000,  regeneration  taking  place  in  the  course 
of  not  less  than  six  weeks.  Other  observers  have  found  little 
or  no  ansemia. 

Hayem3  estimates  the  average  loss  of  red  cells  at  1,000,000. 
In  mild  cases  he  finds  the  lowest  figures  on  the  first  day  of 
normal  temperature.  In  severer  cases  in  which  the  fever  comes 
down  slowly,  the  red  cells  may  not  reach  their  minimum  till 
twenty-four  hours  after  reaching  the  normal  temperature. 

Felsenthal4  in  six  cases  found  the  count  to  be  4,500,000  to 
5,500,000 — no  considerable  variation  from  normal. 

Zappert 5  in  six  cases  found  it  to  be  from  3,920,000  to  4,- 
500,000,  an  average  of  4,150,000. 

White  Cells. — Most  observers  are  agreed  that  leucocytosis  is 
the  rule,  contrasting  in  this  respect  with  measles,  in  which  no 
leucocytosis  occurs.  The  increase  may  be  present  even  six  days 
before  the  rash  appears  and  attains  its  maximum  two  or  three 
days  after  the  eruption.  In  light  cases  it  may  sink  to  normal 
even  before  the  fever  is  gone,  while  in  severer  cases  it  may  per- 
sist several  days  after  a  normal  temperature  is  reached.  Von 
Limbeck  had  a  case  in  which  the  leucocytosis  persisted  for 

1  Dent.  Arch.  f.  klin.  Med.,  vol.  23. 

2  Ref.  in  Petersburg,   med.  Woch.,  1892,  1. 

3  Loc.  cit.,  p.  914. 

4  Arch.  f.  Kinderheilk.,  1892,  p.  80. 
6Zeit.  f.  klin.  Med.,  1893,  p.  292. 


204  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

twelve  days  after  the  temperature  had  become  normal.  Forty 
thousand  per  cubic  millimetre  is  not  unusual  in  well-marked 
cases.  Rieder's  ten  cases  averaged  17,500;  Felsenthal's  six 
counts  were  between  18,000  and  30,000.  My  own  are  simi- 
lar. 

In  a  general  way  the  severest  cases  are  apt  to  have  the  high- 
est leucocyte  counts ;  the  figures  have  no  direct  relation  to  the 
amount  of  fever,  glandular  swelling,  or  to  complications  in  the 
ear  or  kidney. 

Qualitative  Changes. — The  polymorphonuclear  forms  are  in- 
creased, often  to  90  per  cent,  soon  falling  except  in  the  worst 
cases.  The  peculiar  characteristic  of  the  disease  is  the  persis- 
tence of  eosinophiles  in  all  but  the  severest  cases  despite  the 
increase  of  polymorphonuclear  forms.  They  may  run  as  high 
as  5  per  cent  during  the  fever,  and  are  still  more  numerous  in 
convalescence,  remaining  increased  for  six  weeks.  According 
to  Kotschetkoff,  disappearance  of  eosinophiles  is  a  bad  prog- 
nostic sign  except  at  the  very  beginning  of  the  fever,  when  they 
may  be  temporarily  absent  in  favorable  cases.  Presumably 
they  have  some  connection  with  the  exanthem,  eosinophilia 
being  so  common  in  connection  with  skin  lesions.  They 
may  number  15  per  cent  of  the  leucocytes  in  convalescence. 
Felsenthal's  average  is  5  per  cent;  Zappert's,  3  per  cent.  The 
lymphocytes  are  decreased  proportionately  to  the  severity  of 
the  case,  the  worst  cases  showing  only  2  to  4  per  cent. 

An  increase  of  eosinophiles  during  a  scarlatinal  nephritis  is 
regarded  by  Neusser  and  his  pupils  as  a  favorable  sign,  and 
their  absence  as  ominous.  In  ordinary  cases  without  nephritis 
they  reach  their  maximum  in  the  second  or  third  week  and  are 
not  normal  till  the  sixth. 

Summary. 

Moderate  anaemia. 

Leucocytosis  beginning  before  the  eruption  and  often  lasting 
into  convalescence. 

Eosinophiles  said  to  be  increased  in  favorable  cases,  absent 
in  bad  cases. 


MEASLES. 

Diagnostic  and  Prognostic  Value. 


205 


1.  The  chief  importance  of  the  blood  examination  is  in  dis- 
tinguishing the  disease  from  measles  and  the  eruptions  of  other 
diseases.     Measles  has  no  leucocytosis. 

2.  Whether  the  prognostic  significance  attached  by  Neusser 
and  others  to  the  percentage  of  eosinophiles  is  genuine  or  not 
cannot  as  yet  be  positively  stated. 


MEASLES. 

In  mild  cases  the  blood  shows  no  changes  at  all.  Where 
bronchitis,  coryza,  and  conjunctivitis  are  very  marked,  fibrin 
may  be  increased. 

Bed  Cells. — In  mild  cases  no  change — never  over  400,000  or 
500,000  red  cells  are  lost  (Hayem).  Felsenthal's  eight  cases 
showed  counts  of  5,000,000  to  5,500,000. 

White  Cells. — In  most  cases  there  is  no  increase.  Felsenthal 
in  eight  cases  found  the  count  normal  or  diminished.  Pee 
found  but  4,000  in  a  case  with  a  fever  of  102.7°.  Eieder's  eight 
cases  averaged  7,500,  being  lowest  at  the  height  of  the  disease 
and  increasing  as  fever  passed  off.  Complication  with  catarrhal 
pneumonia  or  a  very  bad  bronchitis  and  coryza  may  slightly 
raise  the  count.  The  eosinophiles,  contrary  to  the  example  of 
scarlet  fever,  are  often  absent  during  fever. 

The  Massachusetts  Hospital  records  furnish  the  following 
counts : 

TABLE  XII. —MEASLES. 


Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

\ 

Remarks. 

38 

8 

M. 
M 

4,700,000 

9,000 
9,000 

65 

"  Black  measles"  petechise. 
Differential  count  normal. 

9,8 

F 

8,000 

68 

104°  ;  eruption  out. 

4 
10 

M. 
M 

5,000,000 

7,000 
6,000 

60 

Eruption  just  out. 
103°,  three  days  before  the  erup- 

53 
33 

F. 
F 

6,000 
6,000 
3,500 
3,500 

67 

tion  ;  differential  count  normal. 
Eruption  out  one  day. 
Eruption  out  three  days. 



Felsenthal   found   the   polymorphonuclear  cells   much    in- 


206  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

creased  and  eosinophiles  never  over  one  per  cent.  In  my  own 
cases  the  differential  counts  were  normal.  The  value  of  the 
blood  examination  is  considerable  in  excluding  scarlet  fever, 
diphtheria,  and  syphilitic  roseola,  all  of  which  show  leucocyt- 
osis.  It  cannot  apparently  be  distinguished  by  the  blood  count 
from  Eotlidn  (German  measles),  in  two  cases  of  which,  seen 
at  the  Massachusetts  Hospital,  the  white  cells  were  6,000  and 
8,000  respectively. 

MUMPS. 

Five  cases  of  mumps  under  my  care  showed  no  leucocytosis. 
WHOOPING-COUGH. 

A  girl  of  six  recently  seen  showed  at  the  height  of  the  dis- 
ease 12,600  leucocytes  with  78  per  cent  of  haemoglobin. 

SMALL-POX  (VARIOLA). 

Red  Cells. — According  to  Hay  em  no  other  fever  Is  so  de- 
structive of  red  cells.  During  the  fever  the  count  is  normal  or 
increased,  but  when  the  temperature  falls  permanently  the  num- 
ber of  red  cells  falls  suddenly,  whether  because  the  blood  is 
diluted  (see  above,  page  158)  or  by  a  real  destruction.  From 
this  time  on  the  cells  are  slowly  regenerated;  even  at  the 
fifteenth  day  Hayem  found  them  considerably  below  normal. 

In  hemorrhagic  cases  the  anaemia  comes  on  more  quickly, 
its  degree  depending  on  the  amount  of  hemorrhage.  In  one 
case,  dying  on  the  seventh  day  of  the  eruption,  Hayem  found 
but  2,000,000  red  cells,  in  another  at  the  same  stage,  4,600,000. 

Fibrin  is  not  increased  until  the  stage  of  suppuration  is 
reached. 

White  Corpuscles. — Pick,  who  carefully  studied  42  cases, 
found  that  the  very  lightest  cases,  such  as  occur  in  vaccinated 
persons,  may  cause  no  leucocytosis.  In  a  woman  of  twenty- 
two  on  the  third  day  of  illness  with  a  temperature  of  105°,  the 
count  was  only  4,200  and  on  the  fifth  day  (temperature  99°) 
3,600.  This  patient  had  been  vaccinated. 

Severe  cases  if  without  complication  show  no  leucocytosis 
till  the  pus  appears  in  the  vesicles,  and  after  this  period  the  leu- 
cocytosis slowly  sinks  again.  For  example,  on  the  fifth  day  of 
the  illness,  leucocytes  4,200;  at  the  beginning  of  suppuration, 


ACUTE  ARTICULAR  RHEUMATISM.  20? 

11,600  (eighth  day) ;  at  the  height  of  suppuration  (tenth  day), 
17,200;  at  the  thirteenth  day,  pustules  drying  up,  leucocytes 
7,600. 

In  the  severest  types,  the  leucocytes  follow  about  the  same 
course,  there  being  no  leucocytosis  whatever  in  the  initial  or 
eruptive  stages.  Only  when  the  infection  with  pus  organisms 
begins  do  the  leucocytes  rise,  the  poison  of  variola  itself  having 
apparently  no  tendency  to  increase  the  count.  The  amount  and 
duration  of  the  increase  at  the  stage  of  suppuration  is  in  a  gen- 
eral way  proportional  to  the  severity  of  the  case.  Widal '  has 
recently  found  virulent  streptococci  in  the  blood  in  six  cases  of 
variola. 

VARICELLA    (CHICKEN-POX). 

The  only  observation  of  which  I  am  aware  is  that  reported 
by  Engel.2  In  a  child  of  five  he  found  during  the  height  of  the 
pustular  stage  a  moderate  leucocytosis,  with  67  per  cent  of 
neutrophiles  (high  for  a  young  child),  and  no  eosinophiles. 
Three  days  later  as  the  pustules  were  healing  the  neutrophiles 
had  sunk  to  47  per  cent  (normal  for  that  age)  and  the  ecsino- 
philes  had  risen  to  16  per  cent. 

The  same  conditions  obtain  after  vaccination. 

ACUTE   ARTICULAR  RHEUMATISM. 

According  to  Hayem  and  Garrod 3  the  blood  constitutes  as  in 
syphilis  a  most  valuable  measure  of  the  intensity  of  the  sickness, 
which  is  parallel  to  the  severity  of  the  blood-changes  rather 
than  to  the  number  of  joints  affected.  The  fever,  the  intensity 
of  the  lesions,  and  the  state  of  the  blood  run  parallel,  in  a  gen- 
eral way,  but  the  degree  of  anaemia  is  a  more  delicate  index  of 
the  patient's  condition  than  even  the  temperature  chart  (Garrod). 

The  Blood  as  a  Whole. 

Fibrin  is  greatly  increased.  In  no  other  disease  except  in 
pneumonia  is  the  network  thicker  or  more  rapid  in  formation. 
According  to  Maclagan,  this  is  to  be  explained  by  an  increase  of 

1  Widal :  Centralb.  fur.  allg.  Path. ,  etc. ,  1896,  p.  569. 

2 15th  Cong,  fur  innere  Med.,  1897. 

3  British  Medical  Journal,  May  28th,  1892. 


208  SPECIAL   PATHOLOGY    OF    THE   BLOOD. 

tissue  metamorphosis.  Coagulation,  on  the  other  hand,  is  not 
quicker  but  slower  than  usual. 

Lactic  acid  is  present  in  excess,  but  cannot  be  clinically  es- 
timated, nor  is  its  excess  peculiar  to  this  disease. 

The  alkalinity  of  the  blood  had  been  reported  diminished,  but 
the  technique  is  not  considered  reliable  by  the  best  observers. 

Red  Cells. — Hay  em '  and  Osier 2  state  that  the  poison  of  acute 
rheumatism  is  a  powerful  and  rapid  destroyer  of  red  cells.  In 
acute  cases,  according  to  Hayem,  the  red  cells  lose  at  least 
1,000,000  of  their  number  and  in  cases  which  drag  along  and  re- 
lapse the  loss  is  from  1,500,000  to  2,000,000.  When  an  attack 
is  cut  short  by  salicylate  treatment  the  drain  on  the  corpuscles 
is  stopped. 

So  far  as  can  be  judged  from  the  figures  in  Table  XIII.  of 
the  Masachusetts  Hospital  cases  this  diminution  does  not  seem 
to  occur  in  all  cases.  Many  of  these  cases  had  been  sick  some 
weeks  before  the  time  when  the  count  was  made,  yet  the  counts 
are  not  very  low.  In  the  eight  cases  which  have  been  sick  over 
twenty  days,  the  average  of  red  cells  is  4,462,000;  in  those  sick 
between  one  and  twenty  days,  4,540,000;  and  in  the  whole  group 
of  cases,  4,400,000.  The  lowest  count  was  3,608,000.  Accord- 
ing to  Haj^em  4,000,000  is  the  usual  count  in  acute  cases  and 
3,000,000  to  3,500,000  in  those  which  drag  on  and  relapse. 

Qualitative  Changes. — Maragliano's  so-called  degenerative 
changes  in  the  red  cells  have  been  observed  in  this  disease,  but 
are  not  very  marked.  Deformities  and  nucleated  corpuscles 
appear  only  when  the  anaemia  is  very  marked. 

Haemoglobin. — As  in  all  secondary  anaemias  the  corpuscles 
get  thin  and  pale  before  they  die,  and  hence  the  coloring  matter 
is  diminished  more  than  the  count.  The  average  haemoglobin 
percentage  in  this  series  is  sixty -seven,  and  the  color  index  .76. 
Hayem  noted  that,  in  some  cases  during  convalescence,  as  the 
red  corpuscles  slowly  increase  tfae  color  index  remains  low  or 
even  goes  lower  still. 

Leucocytes.  — All  observers  agree  that  leucocy tosis  is  the  rule 
and  that  its  degree  is  roughly  parallel  to  the  acuteness  and 
severity  of  the  attack  (the  individual's  vigor  of  reaction  is  al- 
ways a  factor)  and  the  amount  of  fever.  The  following  tables 
illustrate  the  variations  of  the  leucocytes  in  a  fairly  typical  way : 
1  Loc.  cit.,  p.  917  »  "Practice  of  Medicine,"  1895. 


ACUTE   ARTICULAR   RHEUMATISM. 


209 


TABLE  XIII.,  A.— ACUTE  ARTICULAR  RHEUMATISM. 


1 

c 

fc 

Age. 

W 

% 

Duration. 

Degree  of 
inflammation. 

Red  cells 

White 
cells. 

Per  cen 
haemo- 
globin. 

Remarks. 

- 

50 

F 

17  days. 

Red  and  hot. 

9 

39,000 

65 

j 

21 

M. 

5  weeks. 

? 

4,160',000 

31,500 

65 

Knees  and  1  ankle. 

59 

F. 

? 

9 

5,476,000 

27,000 

94 

Patient  pale. 

^ 

Adult 

31. 

9 

9 

9 

25,900 

? 

{ 

33 

31. 

2  weeks. 

Red  and  hot. 

4,852,000 

24,500 

76 

b 

20 

F. 

? 

? 

? 

22,400 

? 

Acute  endocarditis 

also. 

J 

Adult 

31. 

? 

? 

4,216.000 

21,000 

56 

8 

23 

31. 

4  weeks. 

Tender  and  hot. 

5,192,000 

18,300 

70 

Temperature  102°. 

9 

10 

28 
19 

31. 
31. 

3       " 
4  days. 

? 
Red  and  hot. 

9 
? 

17,800 
17,400 

? 
? 

Many  joints  affected. 

11 

49 

31. 

? 

? 

4,800,000 

17,700 

? 

Paronychia  also. 

12 

49 

31. 

? 

? 

9 

17,100 

? 

Dec.  2d. 

13 

21 

F. 

? 

Red  and  hot. 

3,944^000 

17.000 

45 

Cheeks  rosy. 

14 

24 

31. 

2  days. 

? 

4,600.000 

16,000 

68 

18 

24 

31. 

? 

? 

4,670,000 

15,500 

68 

16 

35 

31 

15,200 

45 

17 

18 

13 
12 

F. 

31. 

1  day.' 
2  weeks. 

Red  and  hot. 

4,880,000 
4,400,000 

15,200 
15,000 

65 
56 

Temperature  102°. 

19 

19 

31. 

4  days. 

"        " 

4,760,000 

14,500 

75 

Severe  case. 

20 

9 

F. 

? 

v 

4,240,000 

14,386 

-     60 

81 

9 

F. 

" 

Red  and  hot. 

9 

14,050 

9 

22 

47 

31. 

Iday. 

4,750',000 

14,000 

72 

One   joint    only  af- 

fected. 

as 

25 

F. 

3  days. 

Tender  and  hot. 

4.850,000 

14,000 

75 

24 

18 

F. 

2  months 

No    redness      or 

4,156,000 

14,000 

54 

heat. 

25 

19 

31. 

? 

9 

4,172,000 

14,000 

70 

as 

19 

31. 

? 

? 

4,580,000 

13,500 

64 

Nov.  10th,  1895. 

27 

21 

F, 

Iday. 

Red  and  hot. 

9 

13,500 

? 

XJK 

29 

M. 

V 

? 

4,320^000 

12,750 

68 

29 

9 

? 

? 

? 

4,128,000 

12,650 

65 

Dec.  1st,  1895. 

30 

87 

F. 

1  mouth. 

Swollen,  tender. 

5,320,000 

12,500 

64 

SI 

28 

31. 

? 

"               u 

5,000,000 

12,500 

65 

33 

32 

31. 

? 

? 

9 

12,100 

? 

Purpura  also. 

3S 

30 

F. 

9 

9 

4,160',0  0 

12000 

9 

31 
35 

47 
27 

31. 
F. 

4  weeks. 
3  days. 

Very  slight. 

4,288,000 
3,880,000 

12.000 
11,600 

65 
65 

3<; 

17 

3[. 

1  week. 

"      "        " 

4,600,000 

11,500 

70 

Mild  case. 

37 

27 

31. 

10  days. 

Hot  and  red. 

4,200,000 

11,500 

60 

ss 

33 

31. 

4  weeks. 

? 

5,480,000 

11,000 

80 

Hands     alone    i  n  - 

volved. 

39 

18 

31. 

? 

Not  red  and  hot. 

? 

10,000 

.... 

One  joint   only   af- 

fected. 

40 

28 

31. 

3  weeks. 

u          u             u 

3,608.000 

7,000 

40 

41 

Adult. 

31. 

? 

9 

3,768,000 

6,800 

42 
43 

29 

30 

31. 
F. 

9  weeks. 
? 

Some  joints  hot. 
? 

4,104,000 
3,440,000 

5,500 
4,700 

'58 
26 

Tourth  relapse. 
Specific      gravity 

1040. 

Average  — 

4,400,000+ 

6,800+ 

67 

TABLE  XIII.,  B.— SUBACUTE  ARTICULAR  RHEUMATISM. 


No 

Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

1 
2 
3 
4 
5 
6 

25 
30 
28 
28 
Adult. 

M. 
F. 
F. 
F. 
M. 
F. 

4,750,000 
4,644.000 

9 

4,684,000 
4,016,000 
4,188,000 

15,000 
13,000 
10,600 
8,000 
6.200 
5,750 

60 
63 
? 
75 
41 
73 

Ave 

rage  = 

4,400,000 

9,760 

62 

14 


210 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


TABLE  XIII. ,  C. — CHRONIC  RHEUMATISM,  CHIEFLY  ARTICULAR. 


No. 

1 
2 
3 
4 
5 
6 

Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
hemoglobin. 

78 
19 
32 
58 
30 
20 

F. 
F. 
F. 
M. 
F. 
M. 

9 

5,248,000 
? 
4,744,000 

5,576,000 

7,200 
8,300 
6,400 
6,500 
6,100 
9,800 

? 
45 

? 
60 
? 
62 

Average  = 

7,400 

TABLE  XIII.,  D.— MUSCULAR  RHEUMATISM. 


No. 

1 
2 
3 

4 
5 
6 

Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

Remarks. 

46 
54 
38 
54 
27 
35 

M. 
M. 
M. 
M. 
F. 
M. 

4,580.000 
4,360,000 
? 
3,820,000 

? 

7,500 
7,500 
6,600 
14,000 
6,000 
5,700 

70 

75 
? 
58 
? 

During  febrile  attacks. 
Lumbago. 

Average  = 

7,500+ 

The  average  leucocytosis  in  the  acute  cases  is  16,800 ;  in  those 
mild  and  more  chronic,  so-called  "  subacute"  cases  the  leuco- 
cytes range  lower,  averaging  9,760;  while  in  chronic  rheuma- 
tism, whether  articular  or  muscular  (including  lumbago),  there 
is  no  increase  at  all  (average  =7,450). 

In  five  cases  of  arthritis  deformans  treated  at  the  Massa- 
chusetts Hospital  the  blood  was  normal  except  for  a  slight  de- 
ficiency of  haemoglobin  in  two  cases. 

Summary. 

Anaemia  with  leucocytosis,  the  degree  of  which  is  a  measure 
of  the  severity  of  the  infection.  Fibrin  much  increased. 

Diagnostic  Value. 

The  blood  tells  us  little  if  anything  that  could  not  be  learned 
in  other  ways.  It  does  not  differ  at  all  from  that  of  a  septic 
arthritis,  or  from  that  of  acute  gonorrhoeal  arthritis. 

The  only  cases  that  I  remember  in  which  a  blood  examina- 
tion has  been  valuable  are  the  following : 


ASIATIC   CHOLERA.  211 

CASE  I. — The  patient  had  muscular  pains,  fever,  and  a  his- 
tory of  a  malarial  attack  some  months  earlier.  The  question 
to  be  decided  by  the  blood  examination  was  between  malaria 
and  "  rheumatism."  The  leucocytes  were  23,600  per  cubic  milli- 
metre, which  made  it  clear  that  the  case  was  neither  malaria 
nor  "rheumatism,"  since  the  former  never  increases  the  leuco- 
cytes and  the  latter  could  only  give  so  high  a  count  in  case 
genuine  articular  inflammation  were  present.  The  case  turned 
out  to  be  croupous  pneumonia  which  the  high  leucocyte  count 
strongly  suggested. 

CASE  II. — Patient  presented  symptoms  and  signs  of  acute 
polyarticular  rheumatism  with  fever.  The  fever  came  down 
under  salicylates,  but  soon  rose  again,  and  the  man  became 
wildly  delirious.  His  delirium  persisted  after  the  salicylate 
was  stopped.  Several  joints  continued  swollen  and  tender.  The 
fever  was  very  moderate,  ranging  between  99°  and  101°.  There 
were  no  rose  spots  and  no  spleen.  The  question  arose  as  to 
whether  it  was  a  case  of  sepsis  with  localization  in  the  joints,  or 
whether  it  was  a  case  of  typhoid  supervening  on  an  arthritis  of 
some  kind.  The  blood  count,  which  was  repeated  several  times, 
always  showed  a  perfectly  normal  blood  except  for  a  slight  an- 
aemia. The  subsequent  course  of  the  case,  during  which  he  re- 
mained for  nearly  three  weeks  more  or  less  delirious,  made  it 
clear  to  Dr.  F.  C.  Shattuck,  under  whose  care  the  patient  was, 
that  the  diagnosis  was  typhoid. 

Chronic  rheumatism  (muscular  or  articular)  produces  no 
constant  blood  changes  appreciable  by  clinical  methods  (see 
Table  XIII. ,  C  and  D). 

ASIATIC  CHOLERA. 

In  no  other  disease  so  far  as  I  am  aware  has  an  acid 
reaction  in  the  blood  been  reported.  This  is  at  the  end  of 
life.  All  observers  agree  that  the  alkalinity  is  at  least  greatly 
reduced. 

Our  knowledge  of  the  corpuscles  is  best  summed  up  in 
Biernacki's  !  study  of  thirty -eight  cases. 

Red  Cells. — In  the  stadium  algidum,  or  stage  of  collapse,  most 
of  the  symptoms  are  due  to  the  great  concentration  of  the  blood 
from  the  loss  of  serous  fluid  in  the  stools.  Hay  em  found  the 
increase  of  red  cells  from  this  concentration  to  amount  to  from 
1,000,000  to  1,500,000  per  cubic  millimetre. 

Biernacki '  found  7,662,500  in  one  case  twenty-four  hours 
'Deut.  med.  Woch.,  1895,  No.  48. 


212  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

after  the  beginning  of  the  disease.  The  specific  gravity  may  be 
as  high  as  1071  or  1072. 

White  Cells. — Leucocytosis  is  present,  not  merely  as  the 
result  of  concentration,  but  as  a  genuine  increase  to  at  least 
double  the  normal  count.  Biernacki  found  that  cases  with  par- 
ticularly high  counts  (40,000  to  60,000)  were  soon  fatal,  so  that 
he  considers  a  marked  leucocytosis  in  the  algid  stage  as  a  bad 
prognostic  sign,  although  patients  also  die  with  low  leucocyte 
counts  in  this  period.  Such  a  leucocytosis  does  not  occur  in 
ordinary  diarrhoea  or  dysentery. 

Leucocytosis  is  present  as  early  as  twelve  hours  from  the 
first  symptom  and  lasts  at  least  as  late  as  the  sixth  day.  In  the 
stage  of  reaction  it  usually  decreases.  In  one  very  mild  case 
reported  by  Biernacki  there  was  not  only  no  increase,  but  leu- 
copenia  (4,375  per  cubic  millimetre). 

The  differential  count  shows  from  eighty -two  to  ninety-five 
per  cent  of  adult  cells  and  a  corresponding  diminution  of  the 
young  forms. 

ERYSIPELAS. 

Halla,  Pee,  Beinert,  Bieder,  and  v.  Limbeck  agree  that  leu- 
cocytosis is  usually  present  in  well-marked  cases.  Yon  Lim- 
beck finds  the  "leucocyte  curve"  to  run  roughly  parallel  with 
the  temperature  chart,  sometimes  beginning  to  fall  a  little  before 
the  latter.  The  counts  rarely  run  very  high,  yet  Beinert 
counted  39,627  in  one  case.  Pee  noted  that  the  leucocyte  count 
increases  only  while  the  process  is  spreading  and  that  the  size 
of  the  count  was  a  tolerably  accurate  measure  of  the  severity  of 
the  case. 

Bieder  found  in  seven  cases  an  average  of  only  15,000  per 
cubic  millimetre  despite  very  high  temperatures.  In  one  case 
the  leucocyte  count  remained  high  after  the  temperature  had 
fallen,  but  in  the  others  it  anticipated  the  temperature.  In  one 
mild  case  he  found  no  leucocytosis.  Polymorphonuclear  cells 
are  greatly  increased  as  in  other  forms  of  leucocytosis.  Hay  em 
noticed  the  same  dependence  of  the  leucocyte  count  upon  the 
severity  of  the  process. 

.  In  six  cases  at  the  Massachusetts  General  Hospital  I  found 
17,000,  14,000,  13,000,  12,700,  7,250,  and  6,200,  the  last  two 


TONSILLITIS  (FOLLICULAR). 


213 


very  mild  cases.     The  count  of  leucocytes  seemed  proportional 
to  the  severity  of  the  affection. 

When  the  disease  occurred  in  "scrofulous"  cases,  Hayem 
found  only  7,000-8,000  leucocytes  per  cubic  millimetre,  while 
in  cases  with  very  extensive  process  and  high  fever  12,000-20,000 
were  present.  He  found  also  a  loss  of  500,000-1,000,000  in  the 
count  of  the  red  cells,  according  to  the  severity  of  the  case. 
This  showed  itself  particularly  just  before  the  fall  of  the  tempera- 
ture. I  have  seen  no  reference  by  other  writers  to  the  condition 
of  the  red  cells  in  this  affection. 


TONSILLITIS    (FOLLICULAR). 

Halla,1  Pick,2  and  Pee3  found  leucocytosis  as  a  rule  in  un- 
complicated follicular  tonsillitis;  Rieder  found  it  in  a  case 
complicated  with  acute  nephritis. 

The  following  table  confirms  these  observations  in  the  main, 
though  in  mild  cases  no  leucocytosis  was  present. 
TABLE  XIV.— TONSILLITIS. 


o" 
£ 

Age. 

1 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

22 

F. 

4,368,000 

19,200 

35 

2 

21 

F. 

18,000 

8 

27 

M. 

18,000 

4 

21 

F. 

16  800 

5 

25 

F. 

16,200 

6 

30 

F. 

4,  750,  000 

16,000 

80 

Temperature  101°. 

r? 
i 

27 

M. 

4,556,000 

15,500 

67 

Six  days  ;  slight. 

8 

Adult. 

F. 

4,860,000 

14,000 

Follicular. 

1) 

30 

M. 

4,730,000 

13,500 

76 

Convalescent. 

10 

24 

F. 

5,000,000 

13,500 

68 

Follicular. 

11 

Adult. 

M. 

13,500 

12 

M. 

4,952,000 

12,250 

94 

18 

'24' 

F. 

5,816,000 

11,900 

65 

Streptococcus  ;     slight  ar- 

ticular rheumatism. 

14 

M. 

5,000,000 

11,800 

90 

Follicular. 

15 

19 

F. 

4,552,000 

11,600 

52 

16 

18 

M. 

5,150,000 

11,500 

83 

Chronic  recurrent;  out  in 

two  days. 

17 

22 

F. 

5,016,000 

9,600 

IS 

Adult. 

F. 

4,200,000 

5,800 

60 

Follicular. 

19 

23 

F. 



7,925 

52 

Follicular  ;    slight  ;    t  e  m  - 

perature  99°  next  day. 

20 

45 

F. 

6,800 

1  Zeitschrift  f.  Heilkunde,  1883,  p.  198. 

2  Prag.  med.  Woch.,  1890,  p.  303. 

3  Pee:  Inaug.  Dissert.,  Berlin,  1890,  p.  8. 


214  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

The  blood  examination  has  no  diagnostic  value  so  far  as  I 
am  aware.  It  is  worth  knowing  that  a  simple  tonsillitis  can 
cause  leucocy  tosis,  to  the  end  that  if  such  is  discovered  on  blood 
examination  we  need  not  suppose  that  some  other  process  is 
present  to  account  for  the  increase. 

GRIPPE. 

The  references  in  literature  to  the  blood  of  grippe  are  very 
scanty.  Orion  (Archiv.  d.  Med.  milit.,  1890,  p.  280)  found  fibrin 
increased  during  the  early  days  of  the  disease.  Eieder  (Munch, 
med.  Wocli.,  1892,  XXXIX.)  found  no  leucocy tosis  in  grippe 
and  but  little  in  the  "  catarrhal  pneumonia"  following  it. 

The  following  table  shows  that  the  leucocytes  are  normal  in 
at  least  five-sixths  of  the  cases.  Only  eleven  of  the  sixty-seven 
cases  showed  leucocytosis,  and  in  one  or  more  of  these  some 
complication  was  very  possibly  present.  This  is  of  importance 
in  excluding  pneumonia  and  focal  inflammatory  conditions.  The 
leucocyte  count  does  not  help  us  to  distinguish  the  disease  from 
typlioid.  In  this  decision  the  serum  reaction  is  our  mainstay 
(see  below,  page  400).  From  malaria  it  may  be  distinguished 
by  the  absence  of  malarial  organisms.  In  one  case  after  an 
operation  for  traumatic  epilepsy,  the  temperature  rose  to  104°, 
with  a  chill,  and  the  question  of  meningitis  was  considered. 
The  absence  of  leucocytosis  excluded  the  meningitis,  and  the  at- 
tack turned  out  to  be  grippe,  which  was  just  then  very  prevalent. 

TABLE  XV.— GRIPPE. 

White  cells. 

Between    8,000  and    3,000—  lease. 

3,000     "      4,000=  3  cases. 

4,000     "      5,000=  6      " 

5,000    "      6,000=  5      " 

6,000     "      7,000=  14      " 

7,000    "      8,000=  5      " 

8,000    "      9,000=  6      " 

9,000     "    10,000=  9      " 

10,000     "    11,000=  7      " 

11,000     "    12,000=  3      " 

12,000     "    14,000=  8      " 

.  67      " 


SEPTIC^MIA.  215 

TABLE  XV.— GRIPPE. 

Red  cells. 

Between  3, 000, 000  and  4, 000, 000  =     2  cases. 
4,000,000    "    5,000,000=     9      " 
5,000,000    "     6,000,000=  14      " 

25      " 
SEPTICAEMIA. 

Puerperal  septicaemia,  infected  wounds,  septic  arthritis, 
septic  endocarditis,  general  infections  with  pyogenic  bacteria, 
"pyaemia,"  are  all  identical  so  far  as  their  effects  on  the  blood 
are  concerned,  and  will  be  considered  together  under  the  general 
head  of  Septicaemia. 

Bacteriology  of  the  Blood. 

Cocci  can  be  demonstrated  in  cultures  from  the  blood  of  sep- 
ticaemia more  frequently  than  in  any  other  class  of  infections. 
Rosenbach1  in  1884  found  streptococci  and  staphylococci  in 
sepsis.  Garre  2  in  1885  found  the  last-named  coccus  in  a  case  of 
osteomyelitis.  In  1890  v.  Eiselsberg  3  found  staphylococci  in 
ten  cases  of  septic  wounds  and  one  case  of  osteomyelitis,  and 
streptococci  and  staphylococci  together  in  five  more  cases  whose 
wounds  had  become  septic. 

Czerniewsky,4  Stern  and  Hirschler5  found  the  same  organ- 
isms in  puerperal  fever,  the  former  observer  in  five  cases. 

Brunner,6  Hoff,7  and  Blum8  found  pyogenic  staphylococci 
in  pyaemia  and  sepsis,  and  Saenger,9  Eoux  and  Lannois,10 
Cantu/1  and  Bommers  12  had  equal  success,  each  in  a  single  case. 

1  "  Microorganismen   b.  d.  \Vundinfectionskrankheiten,"  pto. .    Wies- 
baden, 1884. 

2  Fortsch.  d.  Med.,  1885,  No.  6. 

3  Wien.  klin.  Woch.,  1890,  No.  30. 

4  Archiv  f.  Gynakol.,  1888,  No.  33. 

5  Wien.  med.  Presse,  1888,  No.  28. 

6  Wien.  klin.  Woch.,  1891,  No.  20. 

7  Dissert,  Strassburg,  1890. 

8  Munch,  med.  Woch.,  1893,  No.  16. 

9  Deut.  med.  Woch.,  1889,  No.  8. 

10  Revue  de  Med.,  1890,  No.  12. 

11  Rif.  Med.,  1892,  No.  96. 

12  Deut.  med.  Woch. ,  1893,  No.  16. 


216  SPECIAL   PATHOLOGY   OF   THE    BLOOD. 

Canon '  and  Sittman  2  investigated  large  numbers  of  cases 
with  many  positive  results,  and  Grawitz 3  and  Petruschky  4  and 
Cohn 5  were  successful  in  finding  pyogenic  cocci  in  the  blood  of 
cases  of  ulcerative  endocarditis  as  well  as  in  other  septic  infec- 
tions. Herschlaff  1B  found  them  in  erysipelas,  acute  tuberculosis, 
perforated  typhoid  ulcer,  etc.  Kiihnan, ly  on  the  other  hand,  was 
unable  to  find  anything  in  the  blood  of  twenty-three  severe 
pyaemic  cases,  and  was  successful  in  only  one  out  of  twelve  cases 
of  ulcerative  endocarditis. 

Taking  the  results  of  all  these  investigators  together,  it 
seems  evident  that  in  many  cases  of  septicaemia,  blood  cul- 
tures, taken  according  to  the  directions  on  page  35,  show  the 
presence  of  pyogenic  organisms,  and  that  in  many  obscure  septic 
cases  the 'diagnosis  may  be  greatly  facilitated  by  such  an  exam- 
ination. Negative  results  are  of  course  very  far  from  excluding 
septicaemia,  but  positive  ones  are  sometimes  of  great  value  if 
proper  precautions  are  taken  in  the  technique  of  the  examina- 
tion. In  the  diagnosis  of  malignant  endocarditis,  often  a  most 
difficult  one,  Grawitz  thinks  blood  cultures  are  especially  im- 
portant and  likely  to  prove  positive  when  the  disease  is  present 
(see  Diseases  of  the  Heart,  page  293) . 

Almost  all  observers  agree  that  the  finding  of  pyogenic  cocci 
(except  the  staphylococcus  albus)  in  the  blood  makes  the  prog- 
nosis almost  surely  fatal.  The  toxicity  of  the  blood  is  doubled. 

Bed  Cells. — All  observers  agree  that  very  marked  anaemia  is 
present  in  severe  cases.  Roscher's1  investigations  tend  to  show 
that  the  diminution  in  red  cells  in  septicaemia  is  greater  than  in 
any  other  infective  disease,  and  appears  in  a  shorter  time.  He 
found  such  a  diminution  present  no  longer  than  a  few  hours  from 
the  beginning  of  the  illness.  He  finds  the  amount  of  anaemia 
proportional  to  the  severity  of  the  case,  and  (reckoning  by  means 
of  the  estimated  solid  residue)  concludes  that  whenever  the  blood 
.has  lost  one-quarter  of  its  substance  or  more,  death  follows. 

'Deut.  Zeit.  f.  Chirurg.,  1893,  p.  571. 
2Deut,  Arch.  f.  klin.  Med.,  1894,  p.  573. 

3  Charite-Annalen,  1804,  vol.  10. 

4  Zeit.  f.  Hygiene,  1894,  pp.  59  and  413. 
5Deut.  med.  Woch.,  1897,  No.  9. 
6Sem.  Med.,  1897,  p.  105. 

7  Deut.  med.  Woch. ,  1897,  No.  25. 
8Inaug.  Dissert,  Berlin,  1894. 


SEPTICAEMIA.  217 

He  considers,  therefore,  that  help  as  to  prognosis  is  given  us  by 
the  blood  examination  in  septicaemia. 

The  serum  becomes  very  watery,  partaking  of  the  general 
atrophy  of  the  blood  tissue.  In  a  case  of  intensely  acute  puer- 
peral sepsis  Grawitz  found  the  red  cells  reduced  to  300,000  ( ! ) 
although  the  patient  had  been  sick  less  than  twenty-four 
hours.  The  case  seems  almost  incredible,  but  is  reported  in 
great  detail  in  the  author's  recent  text-book,  to  which  reference 
has  so  frequently  been  made.  He  accounts  for  it  by  the  combi- 
nation of  blood  destruction  and  dilution. 

In  the  nine  cases  of  puerperal  sepsis  seen  at  the  Massa- 
chusetts General  Hospital  in  recent  years  the  red  cells  averaged 
3,780,000,  which  is  very  low,  considering  the  shortness  of  the 
illness  in  most  cases.  (The  influence  of  hemorrhage  during 
parturition  must  of  course  be  taken  into  account.) 

In  most  of  the  septic  wounds  which  I  have  seen  the  counts 
have  not  been  low.  But  in  one  case  of  septicaemia  from  a  sup- 
purating fibroid  of  the  uterus  the  red  cells  numbered  only 
1,800,000.  In  a  case  of  puerperal  sepsis  of  only  a  few  days' 
duration,  in  a  woman  not  previously  anaemic,  Hayem  '  recently 
reports  the  following  figures : 

December  3d— Red  cells 1, 450, 000 

White  cells 7, 500 

Haemoglobin 20  per  cent. 

December  6th— Red  cells 2, 578, 000 

White  cells 8,000 

Haemoglobin 40  per  cent. 

December  24th— Red  cells 4, 231, 000 

White  cells 7,200 

Haemoglobin 65  per  cento 

(Recovery. ) 

Such  cases  are  the  best  examples  we  have  of  an  acute  ancemia 
(hemorrhage  excepted) . 

The  hemoglobin  is  usually  diminished  about  as  much  as  the 
corpuscles.  According  to  Bond  it  tends  to  crystallize  about  the 
edge  of  a  slide  and  cover-glass  preparation  of  the  fresh-blood. 

Deformities  in  the  shape  and  size  of  the  corpuscles  are  not 
usually  present  except  in  the  severest  cases. 

1  La  Med.  Moderne,  January  13th,  1897. 


218 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


TABLE  XVI. — PUERPERAL  SEPTICJEMIA. 


d 
fc 

Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

31 

F. 

77,  500 

Autopsy. 

2 

21 

F. 

2,300,000 

26,000 

3 

29 

F. 

3,900,000 

23,900 

68  * 

Two  days  before  delivery. 

21,000 

. 

Day  of  delivery. 

9,500 

One  day  after  delivery. 

15,500 

.  . 

Five    days   after    delivery; 

breasts  caked. 

15,000 

Ten  days  after  delivery. 

4 

28 

F. 

3,784,000 

11,800 
22,000 

55 

Twenty-six  days  after  delivery. 
Miscarriage   five  days  before  ; 

septic  ;  curetted. 

13,600 

Three  days  later,   temperature 

falling. 

8,300 

Seven  days  later,  temperature 

normal. 

15,800 

Fourteen  days  later,  tempera- 

ture up  ;  curetted  again. 

14,900 

Fifteen  days  later,  temperature 

falling. 

15,000 

Sixteen  days  later,  temperature 

falling. 

9,500 

Thirty-two  days  later,  temper 

ature  falling. 

5 

25 

F 

20  800 

55 

6 

34 

F. 

15,900 

September    2d,  1897. 

35,600 

September    9th,  chills. 

33,000 

September  13th. 

35,  600 

.  . 

September  16th.      Recovered. 

7 

25 

F. 

2,936,000 

20,000 

50 

Ar*il  1st,  1894. 

21,000 

April  3d,  1894. 

8 

32 

F. 

4,904,000 

19,300 

Curetted. 

9,300 

One  week  later,  well. 

9 

24 

F. 

3,556,000 

18,400 

10 

F. 

Marked 

Polymorphonuclear  cells,   94$  ; 

increase. 

lymphocytes,  6$. 

11 

26 

F. 

5,368,000 

5,600 

Died. 

TABLE  XVII.,  A.— SEPTIC  WOUNDS. 


0 

"A 

Age. 

1 

Red  rplls. 

White 
cells. 

Per  cent 
haSino- 
globin. 

Remarks. 

1 
•fl 

37 

28 

F. 
M 

5,880,000 
7  600  000 

48,400 
25  400 



Sloughing  breast  ;  bedsore. 
Septic  wound  of  foot. 

3 

31 

F 

5,680  000 

15  300 

i 

Sloughing    breast    after    cancer 

6,700 

operation. 

5  840  000 

23  200 

One  month  later  •  wound  clean. 

4 

27 

M 

4  450  000 

10  500 

Septic  hand. 

5 

M 

5,600  000 

8  800 

Septic  finger 

SEPTIC^MIA. 


219 


TABLE  XVII.,  B.—  SEPTICJEMIA  WITH  ARTHRITIS. 


Age. 

M 

£> 
02 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

8 

M 

25  000 

Pus  in  6lbow  "joint  *  no  in  "jury 

43,000 

Two  days  after  operation,  vent 

24,  000 

not  free  ;  opened  further. 
Seven  days  after  operation 

20,  700 

Eight  days  after  operation. 

6,700 

Sixteen  days  after   well. 

34 
59 

M. 
M 

4,520,000 

19,000 
18,500 

65 

Gonorrhoeal,  pus  in  knee. 
Pus  in  shoulder  joint,  no  trauma* 

22 

M 

13,800 

Gonorrhoeal  ankle 

39 

M. 

8,940 

Gonorrhoeal  ankle  ;  cultures  neg- 
ative. 

TABLE  XVII.,  C.— GENERAL  STREPTOCOCCUS  SEPTICAEMIA. 


Age. 

1 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

Adult, 
u 

M. 
F. 

5,248,000 
1,800,000 

41,400 
46,000 

Suppurating  fibroid. 

22 

F. 

3,776,000 

25,800 

52 

A  fatal  case,  yet  no  fever  ! 

Hcemoglobincemia  with  reddish  staining  of  the  serum  is  often 
noticeable  in  the  dried  and  stained  cover-glass  specimen  where 
the  plasma  is  deeply  stained. 

Leucocytes. — Considerable  controversy  has  taken  place  as  to 
the  changes  in  the  white  cells  effected  by  septicaemia ;  some  ob- 
servers finding  leucocytosis,  while  others  find  none. 

The  results  of  experimental  infections  referred  to  above  (see 
page  110)  and  the  parallelism  of  the  leucocyte  changes  in  pneu- 
monia, peritonitis,  and  diphtheria  fully  explain  these  appar- 
ent divergences,  which  perfectly  exemplify  the  rules  stated  on 
page  106. 

Leucocytosis  occurs  only  when  the  struggle  between  the  pa- 
tient and  his  disease  is  intense,  and  whichever  is  victorious. 
When  either  side  wins  without  any  difficulty,  i.e.,  in  the  mildest 
and  in  the  severest  cases,  leucocytosis  is  nearly  or  entirely  ab- 
sent ;  indeed,  leucopenia  may  be  found  (as  for  instance  in  a  case 


320  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

of  septic  endometritis  reported  by  v.  Limbeck — only  3,000  leu- 
cocytes). Von  Limbeck  and  Krebs  l  found  no  leucocytosis  in 
cases  of  perpetual  septicaemia,  but  these  were  all  fatal  cases  or 
very  mild  ones.  Bieder,  on  the  other  hand,  and  the  great  major- 
ity of  other  observers  (Sadler,2  Boscher,3  Kanthak,4  Grawitz, 
etc.)  find  leucocytosis.  This  means  that  in  most  cases  ob- 
served by  these  writers  the  infection  was  of  moderate  severity. 
Only  two  of  the  twenty-one  cases  in  Tables  XVI.  and  XVII. 
showed  no  leucocytosis.  One  was  very  mild,  the  other  died  on 
the  day  of  the  count. 


Summary. 

1.  Bapid  development  of  severe  anaemia. 

2.  Leucocytosis  marked,  except  in  very  mild  or  very  severe 
•cases. 

3.  Blood  cultures  often  contain  pyogenic  cocci. 

Diagnostic  Value. 

The  advantage  of  a  positive  bacteriological  examination  is 
obvious.  Of  the  value  of  the  blood  count  in  distinguishing  septic 
from  non-septic  wounds  and  estimating  the  degree  of  sepsis  and 
the  importance  or  needlessness  of  operative  interference,  not 
much  is  known.  The  subject  deserves  to  be  carefully  worked 
out  from  a  surgical  point  of  view.  The  following  cases,  how- 
ever, tend  to  show  that  we  might  utilize  blood  counting  far  more 
than  we  do  to  determine  questions  of  this  sort : 

CASE  I. — Frank  B — —  was  a  case  of  appendicitis  operated  on 
by  Dr.  M.  H.  Bichardson  at  the  end  of  an  attack.  A  little  pus 
was  found,  the  appendix  was  excised,  and.  the  wound  nearly 
closed,  a  small  strand  of  gauze,  however,  being  left  in.  Several 
days  after  the  operation,  there  being  at  the  time  no  external  dis- 
charge, the  temperature  rose.  The  wound  seemed  perfectly 
clean.  The  man  was  very  nervous  about  himself,  and  much 

1  Krebs :   Dissert. ,  Berlin,  1893. 

2  Sadler  :  Lot.  tit. 

8Roscher:  Dissert.,  Berlin,  1894. 

*  Kanthak :  Brit.  Med.  Journal,  June,  1892. 


SEPTIC^MIA.  221 

stirred  up  at  each  dressing ;  and  as  the  temperature  never  went 
higher  than  101°,  there  seemed  to  be  considerable  doubt  as  to 
what  the  cause  of  the  temperature  was.  The  blood  count  in 
this  case  showed  52,000  leucocytes.  On  opening  the  wound  a 
large  amount  of  broken-down  blood  clot  was  evacuated,  and  the 
temperature  came  down  to  normal. 

CASE  II. — Mrs.  S was  a  case  of  pus  tube  shelled  out  and 

sewed  up  tight.  Ten  days  after  the  operation  the  temperature 
began  to  look:  as  if  pus  were  present.  Here  again  the  patient 
was  exceedingly  nervous ;  and,  as  so  often  happens,  the  question 
was  asked  and  re-asked,  whether  she  was  keeping  up  her  own 
temperature  by  the  state  of  her  mind.  The  blood  count,  how- 
ever, showed  marked  leucocytosis,  which  led  to  a  careful  ether 
examination,  revealing  a  fluctuating  mass  behind  the  uterus, 
from  which  pus  was  obtained  by  puncture. 

CASE  III.— Mr.  R entered  the  Massachusetts  General 

Hospital  in  December,  under  the  service  of  Dr.  C.  B.  Porter, 
with  a  compound  fracture  of  the  thigh.  Some  days  after  it  had 
been  put  up,  the  temperature  began  to  suggest  the  presence  of 
pus,  the  wound,  however,  remaining  perfectly  clean.  I  counted 
the  blood,  and  found  a  marked  leucocytosis.  A  more  thorough 
exploration  of  the  wound  revealed  a  pocket  of  pus,  the  evacu- 
ation of  which  brought  down  the  temperature.  I  was  not  sure 
in  this  case  whether  the  absorption  of  the  blood  clot,  such  as 
takes  place,  I  suppose,  after  any  compound  fracture,  would  be 
sufficient  to  cause  leucocytosis.  I  therefore  counted  several 
cases  in  which  there  was  fever  and  presumably  blood-clot  ab- 
sorption, namely,  a  hsemothorax,  a  pelvic  hsernatocele,  two  com- 
pound fractures,  and  a  crushed  foot ;  in  none  of  these  was  any 
leucocytosis  present. 

CASE  IV.— Mr.  S was  operated  on  by  Dr.  J.  C.  Warren  for 

traumatic  epilepsy.  Nothing  special  was  found,  and  the  wound 
was  closed.  Ten  days  after  the  operation  the  temperature  rose 
to  104°,  and  the  patient  complained  of  severe  headache  and  pain 
in  the  back.  I  counted  the  blood,  and  found  no  leucocytosis. 
Next  day  the  temperature  was  down.  The  patient  apparently 
had  the  grippe. 

Several  cases  in  which  an  old  malaria  was  supposed  to  be 
"  brought  out"  by  a  surgical  operation,  the  patient  having  irreg- 
ular fever  and  chills  after  the  operation,  have  shown,  on  exam- 
ination of  the  blood  by  the  writer,  no  malarial  organisms  but 
marked  leucocytosis.  In  these  cases  the  symptoms  of  "  malaria" 
ceased  when  the  wound  was  more  thoroughly  drained,  and  I 
have  no  doubt  that  many  cases  of  "  malaria"  after  surgical  oper- 
ations are  really  wound  sepsis. 


222  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

It  is  difficult  to  make  inferences  from  a  leucocytosis  in  such 
<cases,  because  no  one,  so  far  as  I  know,  has  thoroughly  investi- 
gated the  blood  condition  during  the  normal  healing  process  of 
wounds.  But  there  are  certainly  many  cases  in  which  we  need 
the  kind  of  information  about  the  condition  of  a  wound  which 
the  blood  might  give  us,  if  the  changes  in  connection  with 
wounds  were  better  known. 

How  often  the  questions  are  asked:  Is  this  patient  septic? 
Does  this  temperature  mean  anything  of  importance?  Is  this 
wound  well  drained?  Is  this  complaint  of  pain  hysterical  or 
does  it  mean  something  operable? 

How  often  the  blood  count  would  help  us  to  answer  such 
questions  without  leaving  it  for  time  to  settle  them  after  the 
most  urgent  need  of  settling  them  is  gone,  we  do  not  yet 
know. 

In  puerperal  cases,  the  fact  that  leucocytosis  is  always 
present  for  several  days  after  delivery  makes  it  harder  to  judge 
from  the  blood  whether  a  given  case  is  septic.  I  doubt  if  the 
blood  count  will  give  any  information  on  this  point  not  to  be 
more  easily  obtained  in  other  ways.  Blood  cultures,  if  positive, 
.are  of  far  greater  importance,  but  take  more  time. 

ABSCESS. 

Goldberger  and  Weiss  '  have  recently  described  a  reaction  to 
iodine  in  the  leucocytes  of  the  blood  in  cases  of  local  suppura- 
tion. A  syrupy  mixture  of  the  following  elements  is  made : 

lodi  sublim 1 

Pot.  iodati 3 

Aq.  dest 100 

Gum  mi  ad  syrupam. 

This  is  painted  on  a  slide  and  the  unstained  cover-glass 
preparation  is  pressed  down  into  it.  So  treated  normal  blood 
or  that  of  non-suppurative  diseases  shows  the  following:  red 
cells  dark  yellow ;  white  cells  light  ydlow  with  very  refractile, 
citron  yellow  nuclei. 

In  purulent  affections  the  protoplasm  of  the  leucocytes  stains 
brown,  either  diffusely  or  in  a  granular  or  network  distribution. 
1  Wien.  klin.  Woch.,  1897,  No.  25. 


APPENDICITIS.  223 

After  an  abscess  is  opened  tlie  brown  color  is  at  first  confined  to 
the  periphery  of  the  cell  and  soon  disappears  altogether. 
"  Cold"  abscesses,  no  matter  how  large,  do  not  produce  the  reac- 
tion, but  acute  felons  with  only  a  thimbleful  of  pus  have  shown 
marked  iodine  reaction. 

The  reaction  occurs  also  in  pneumonia  and  in  the  moribund 
3tate. 

The  effects  of  abscess  upon  the  blood  are,  I  suppose,  due  to 
septicaemia.  Nevertheless  septicaemia  with  abscess  formation 
differs  enough  from  septicaemia  without  abscess  formation,  both 
clinically  and  haematologically,  to  make  a  separate  description 
convenient. 

The  most  easily  studied  variety  of  abscess  is  that  connected 
with  appendicitis,  inasmuch  as  the  frequency  of  operations  in 
such  cases  gives  us  opportunity  to  verify  what  we  suppose  to  be 
indicated  by  the  blood  count  and  see  how  far  our  suppositions 
are  true. 

At  the  Massachusetts  General  Hospital,  most  patients  with 
other  varieties  of  abscess  go  straight  to  the  surgeon  and  their 
blood  is  not  examined,  but  many  cases  of  appendicitis  come 
first  to  the  medical  wards,  and  hence  we  have  records  of  over 
eighty  cases  whose  blood  has  been  examined. 

I  shall  therefore  begin  the  description  of  the  blood  in  abscess 
by  an  account  of  appendicitis,  which  may  probably  be  considered 
a  typical  case  of  abscess  formation. 

APPENDICITIS. 

After  excluding  all  cases  in  which  the  diagnosis  was  not  sure 
we  have  left  seventv-two  cases. 


224 


SPECIAL  PATHOLOGY   OF  THE  BLOOD. 


TABLE  XVIII.— APPENDICITIS. 


&  g 

<  $ 

If 

Sv 

11 

Per  cent 
haemo- 
globin. 

43  M 

3  400  000 

52  000 

40  M 

6  800  000 

43  000 

30  F. 

5,'l84,bbo 

39,900 
36.800 

4  gOO  000 

36,000 

50  M. 

4,290,000 
6000000 

35,000 
34,000 

6  500  000 

34000 

?  M. 

5,072,000 

28,000 
24,200 

16,850 
15600 

... 

10,700 

15,100 

14,600 

11,800 

17,850 
18  200 



13  100 

24,000 

12,500 

19,500 

23  M. 
..  M 

5,200,000 
5,144,000 

24,000 
23,000 
16,100 
22,500 

82 

13,000 

9,500 

..  M 

22,300 

35  F 

9,500 
22,000 



.  .  • 

19  400 

14,900 

..  M. 



21,900 
21,700 



21  400 

16,000 
24  400 



20,200 
47,700 

16  700 

13,000 

10,700 

30,300 
20  900 



17,700 
25,100 

28,100 

20,400 

15,400 

25,000 

11  900 

15,600 

21,900 
19,000 
11,900 

12  800 

11  700 

12,300 

15,600 
13,400 



14,700 

16  500 

11,300 

31  M. 



20,540 



Remarks. 


Question  of  typhoid;  pus  found  at  operation. 
Chronic  case;  96  per  cent,  of  adult  leucocytes. 


Three  days  after  operation. 

Second  attack;    operation  at  11  P.M.     November  5th, 

count  at  5:30. 

Serous  peritonitis  found.     November  6th,  5  P.M. 
November  7th,  3  P.M. 

8th,  4     " 

Temperature  still  up.    November  9th,  5  P.M. 
November  10th,  5 :  30  p.  M. 

llth,  8:30  " 

12th,  8:30  " 

13th,  SA.M. 

13th,  8:  30  P.M. 
Recovery  complete  ten  days  later. 
24°  September  1st;  operation,  free  turbid  fluid  without 

adhesions. 
September  10th. 

12th  ;  pocket  of  pus  found. 

January  14th. 

15th;  before  operation,  J,  v.  -f-  pus. 
Not  operated ;  entrance. 
Second  day. 

TVliWl  " 


belly  full  of  pus. 

blood  dark  and  hard  to  get. 


Third 

12:  20  operated 
8 : 30  moribund 
July    6th. 
8th. 

10th,  104°;  recovery. 
Appendicitis  eight  to  nine  days;  operation;  post-caecal 

abscess. 

November   5th,  first  operation. 
10th. 
13th. 
15th. 
16th. 

19th,  second  operation  (pus  pocket). 
20th. 
21st. 
22d. 

26th,  third  operation  (pus  pocket). 
27th. 
28th. 
29th. 
30th. 
December   1st. 
2d. 
3d. 
4th. 
5th. 
6th. 
7th. 
8th. 
9th. 
10th. 
llth. 
12th. 
13th. 
21st. 
25th. 
26th 
October  5th. 


APPENDICITIS. 


225 


TABLE  XVIII. — APPENDICITIS  (Continued). 


&  $ 

<  08 

•e.2 
tfl 

|j 
11 

111 

&sz 

Remarks. 

31   M 

33  000 

October  6th 

14,640 

"       8th 

9,200 
21  000 



"       9th  ;  moved  bowels. 

24,900 

99°  to  100°  temperature 

13700 

Normal'  still  sore 

M 

20  100 

October  23d 

14  000 

"       24th   9AM 

12,400 

"        24th,  4  P.M 

13250 

"        24th   11  P  M  '  not  operated 

8  750 

"       25th  8AM*  liquids  every  two  hours 

24  F. 



9,600 
20,000 
19,000 
20,000 



25th,  SP.M. 
May  24th. 
"    25th. 
June  5th;  temperature,  101.4°;  pain  and  vomiting 

9,000 
10,000 



June  7th;  no  pain. 
"    8th  ;  no  pain  ;  temperature,  100.6°  ;  discharged. 



4,800,000 
5  564  000 

20,000 
20000 



Operated;  pus. 

4.670  000 

19,750 

January  13th 

5,296,000 

15,000 

"        15th. 

20  F. 

19,600 

"        29th 

4,680,000 

12000 

February  1st 

4  688  000 

8933 

"          5th    after  operation 

19,500 

No  operation 

58  M. 
20  M. 
14   M. 

5,120,000 
5,680,000 

19,000 
18,930 
18000 

Purulent  peritonitis. 

17  500 

25   M. 

16  250 

Fifth  day     November  7th 

17450 

November  8th 

12,000 

"         llth;  not  ope  rated;  well  on  17th 

25   M. 

16200 

40  'F.' 



16,200 
16051 



Eighth  day;  operation;  large  abscess  cavity. 
Operated. 



16,000 
8  000 



Entrance. 

7,500 

Next  day 

6800 

6,160,000 

16000 

General  peritonitis 

16,000 
8  000 



November  12th,  noon. 
12th  81  30  p  M 

17  M. 

3,300,000 
4,380,000 

7,500 
6.600 
16,000 
15,600 
^9500 

66 

"          13th,  8  A.M.;  not  operated. 
13th,  8  P.M. 

March  25th,  9  P.M.  ;  vomiting,  pain,  tenderness. 

22,900 
35,300 



localized. 
28th  ;    slight  tenderness  only. 
"      29th  ;  bowels  move  well  •  no  symptoms 

27  M. 
23  M. 
22  M. 

4,330,000 
5,910,000 

32,800 
15,523 
15.330 
14,800 
10,000 

"      30th;  operation;  large  amount  or  pus. 

20th  ;  general  peritonitis. 
21st  ;          "                " 

36   F. 
23  F. 

4.250.000 

14,  700 

14,700 
13,150 
14,400 
10,300 

70 

Five  days  ;   third  attack;  operation;  free  turbid  fluid, 
no  perforation  ;  prompt  recovery. 
27th,  8  P.M. 
28th  ;  symptoms  less  ;  no  operation. 
February  23d,    ^.jfoulpus 



4,950,000 

14,000 
13  400 

Catarrhal. 

5000000 

11,200 
13  000 

5  P.M.,  'November  10th;  temperature,  98.8°. 

13,000 

Visible  tumor     March  27th 

17000 

4,626,000 
1 

12,000 

5 

226 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


TABLE  XVIII. —APPENDICITIS  (Continued). 


II 

If 

•§* 
11 

Per  cent 
haemo- 
globin. 

Remarks. 

M 

12  000 

Appendicitis  cake     August  3d,  operation*  gangrenous 

M 

16,900 
11  900 



appendix  with  adhesions. 
August  6th,  faecal  fistula. 
No  symptoms  except  pain  for  twenty  -four  hours*  not 

51   M. 

11,800 

operated. 
Very   slight    tenderness:     no  resistance  or  dulness. 

19900 

July  6th. 
Temperature  up*  tenderness  and  resistance.    July  7th 

..    M. 

4,860,000 

11,700 
17,600 
16,670 

58 

operation;  pus  found. 
December  28th,  4  p.  M. 
30th,  10A.M. 
"          31st,  11    " 

11  950 

January  1st  9  p  M 

10,800 
10  875 

5th. 
July  27th;  nine  days  pain  and  vomiting 

22   F 

4  664000 

21  000 

July  28th  *  more  pain  tenderness  and  vomiting*  opera- 

10 700 

tion  showed  pus. 
November  7th    appendicitis  six  days 

..    M. 

9000 

Operation;  abscess  with  considerable  pus;  gangrenous 

10,500 

perforated  appendix  with  concretion  in  it. 
Not  operated  till  later. 

12   F 

3  690,000 

10400 

February  6th  12  M.  ;  slight  pain  and  tenderness. 

46  M 

9  800 

"         7th  3  P  M  *  temperature  dropping. 

10,400 

Catarrhal 



5,600,000 

10,500 
10,140 



One  week,  fourth  attack;  no  cake,  no  acute  symptoms; 

..    M. 



10  040 

operation  ;  no  pus. 
Sixth  day   operation  •  abscess,  5  *•  pus. 

.   M. 

9,000 

Operated;  no  pus;  catarfhal. 

..    M. 
24   F 



8,400 
10  000 

December   1st. 
6th 

7,200 

"           15th. 

7,600 

"          16th. 

7,760 

No  pus 

5,106  000 

7  600 

5  600  000 

7  600 

31   M". 
47  M 

6,500,000 
6,500,000 

6000000 

7,6CO 
7.050 
7,000 
6  600 

'"85"" 

No  pus. 
Catarrhal  appendix;  five  days  in  hospital. 
Catarrhal  appendix. 
"         chronic*  nearly  well;  operation;  no  pus. 

56   M. 

6,000 

"         or  very  slight. 

22   F. 

4,320,000 

From  the  seventy-two  cases  of  the  adjoining  table,  together 
with  forty-one  other  counts  not  here  recorded,  the  following 
conclusions  are  to  be  drawn: 

1.  Red  cells :  no  changes  except  in  chronic  cases  with  long- 
standing abscess. 

2.  Coagulation   often  slow,   but  fibrin  always  increased  in 
suppurating  cases. 

3.  As  in  most  infections  the  mildest  and  the  severest  cases 
;show  no  leucocytosis.     Four  cases  witli  general  purulent  peri- 
tonitis showed  no  leucocytosis,  its   absence  being  confirmed  by 
repeated  examinations.     The  total  absence  of  leucocytosis  in  a 
case  not  obviously  mild  is  a  very  bad  prognostic  sign  as  in  pneu- 
monia and  diphtheria. 


APPENDICITIS.  227 

4.  Catarrhal  appendicitis  is  rarely  accompanied  by  leucocy- 
tosis  (only  once  in  this  series — 14,000). 

5.  An  increasing  leucocytosis  means  a  spreading  process  and 
may  be  the  only  evidence  of  the  fact.     In  Case  40  of  this  series, 
the  patient  entered  with  vomiting,   localized  pain  and  tender- 
ness.    The  leucocytosis  was  15,600.     Three  days  later  he  was 
comfortable,  had  no  vomiting  and  very  little  tenderness,  and  in 
all  respects  seemed  to  be  improving,  yet  the  white  cells  had 
risen  to  22,900.     Operation  was  postponed  owing  to  the  lack  of 
all  unfavorable  symptoms  except  the  blood  count.     Next  day  the 
bowels  were  moving  well  and  the  patient  had  no  fever  and  no  bad 
symptoms  of  any  kind,  but  his  leucocytes  had  risen  to  35,300. 
On  the  following  morning  the  surgeon  was  finally  persuaded  to 
operate  and  found  a  large  amount  of  pus. 

A  steadily  increasing  leucocytosis  is  always  a  bad  sign  and 
should  never  be  disregarded  even  when  (as  in  this  case)  other 
bad  symptoms  are  absent.  It  is  of  far  more  significance  than 
a  larger  count  which  does  not  increase. 

6.  The  size  of  the  leucocytosis  is  of  comparatively  little 
significance.      A  low  count  (8,000-11,000)  means  one  of  three 
things : 

(a)  A  mild  case. 

(b*)  A  very  severe  case. 

(c)  An  abscess  thoroughly  walled  off. 

After  the  abscess  has  ceased  to  spread  and  has  become  well 
walled  off,  the  leucocyte  count  remains  stationary  or  decreases. 
If  it  bursts  into  the  general  peritoneal  cavity  the  count  may 
rise  sharply  or  it  may  fall  to  normal  or  subnormal,  its  move- 
ment depending  on  the  degree  of  resistance  which  the  system 
offers. 

7.  In  the  majority  of  cases  the  pus  is  neither  completely 
walled  off  nor  free  in  the  belly,  and  such  cases  are  accompanied 
by  a  moderate  and  fluctuating  leucocytosis,  which  rises  and  falls 
according  to  a  variety  of  conditions  which  cannot  be  accurately 
interpreted. 

It  usually  increases  in  the  first  three  or  four  days  of  the  ill- 
ness, and  then  becomes  stationary  or  declines  if  the  case  is  tak- 
ing a  favorable  course  (i.e.,  if  the  pus  is  being  absorbed  or 
walled  off) ,  while  it  continues  to  increase  when  the  case  is  going 
on  from  bad  to  worse. 


228  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

Case  20  illustrates  the  course  of  the  leucocytes  in  a  favorable 
case  not  operated  on ;  the  leucocytes  fell  gradually  but  steadily 
from  hour  to  hour  so  that  in  two  days  the  count  came  down  from 
20,100  to  8,750,  the  tumor  and  tenderness  simultaneously  dis- 
appeared, and  the  patient  was  well  in  a  few  days  more.  Case  38 
dropped  in  eight  hours  from  16,000  to  8,000  and  quickly  recov- 
ered. In  Case  19,  the  leucocytosis  fell  in  three  days  from  33,000 
to  9,200,  but  rose  again  when  the  bowels  were  moved  by  enema, 
and  took  some  days  to  reach  normal  again.  Evidently  the  per- 
istalsis injured  the  abscess  wall  so  that  the  process  began  to 
spread  again  and  had  to  be  walled  off  afresh. 

8.  When  a  leucocytosis  of  18,000-25,000  is  maintained  for  a 
number  of  days  it  usually  means  a  large  abscess  pretty  well 
walled  off. 

9.  The  majority  of  cases  as  seen  at  the  Massachusetts  Gen- 
eral Hospital  on  the  second,  third,  and  fourth  day  of  the  ill- 
ness  show  leucocytosis   of  15,000-24,000,  thirty -three   of  the 
present  series  falling  within  these  figures.     Counts  larger  than 
this  have  always  been  proved  to  mean  a  large  amount  of  pus  or 
a  general  peritonitis.     Of  the  cases  below  15,000  (fifteen  in  all) 
twelve  did  not  come  to  operation,  or  if  operated  showed  no  pus. 
This  statement  excludes  the  four  cases  of  general  purulent  peri- 
tonitis without  leucocytosis  mentioned  above. 

10.  Case  18  illustrates  several  points.     After  the  first  opera- 
tion the  leucocyte  count  did  not  fall  so  rapidly  as  usual,  and  the 
cause  of  this  soon  turned  out  to  be  a  pus  pocket,  after  the  evac- 
uation of  which  the  count  fell  in  twenty-four  hours  from  47,700 
to  16,700,  only  to  rise  again  for  another  accumulation  of  the 
same  kind. 

After  this  last  (third)  operation  the  case  progressed  slowly 
but  favorably,  and  yet  the  leucocyte  count  remained  more  or  less 
above  normal  for  a  month.  The  wound  was  healthy,  freely  dis- 
charging, and  had  healed  satisfactorily  at  the  time  of  the  last 
count  recorded. 

Whether  all  wounds  follow  this  course  as  regards  the  leu- 
cocytes I  do  not  know.  It  is  an  important  point  which  needs 
working  out,  namely  :  What  is  the  normal  behavior  of  the  blood 
count  during  the  healing  of  granulating  wounds?  If  this  were 
known,  we  might  get  valuable  information  as  to  whether  a 
wound  is  doing  well  or  not,  by  means  of  the  blood  count,  which, 


APPENDICITIS.  229 

if  septic,  would  probably  behave  differently  from  its  wont  in 
wounds  which  do  well.  As  it  is,  all  these  questions  are  not  an- 
swerable. It  is  to  be  hoped  that  surgeons  will  investigate  them. 

Differential  Diagnosis. 

1.  The  presence  of  a  marked  leucocytosis  excludes  simple 
colic  witli  or  without  constipation,  and  excludes  certain  forms  of 
intestinal  obstruction  (if  uncomplicated).     Such  cases  of  intes- 
tinal obstruction  as  are  complicated  with  ulceration  or  gangrene 
or  due  to  cancer  may  raise  the  leucocyte  count. 

Between  general  peritonitis  from  an  appendicitis  and  intes- 
tinal obstruction,  the  presence  of  marked  leucocytosis  points  to 
the  former;  but  its  absence  may  accompany  either  affection.  I 
remember  a  case  in  which  the  diagnosis  lay  between  these  two 
affections,  and  operation  was  delayed  because  the  absence  of  any 
leucocytosis  was  thought  to  rule  out  peritonitis,  and  it  was 
hoped  to  get  the  bowels  started  by  enemata,  etc.  When  finally 
the  abdomen  was  opened  stinking  pus  gushed  out  and  the 
patient  died  the  same  day. 

2.  Treves '  has  reported  several  cases  in  which  it  was  hard 
to  decide  whether  the  diagnosis  was  typhoid  or  appendicitis.     A 
blood  examination  would  probably  have  decided  the  matter  as 
it  has  in  three  cases  in  the  writer's  experience.     Most  cases  of 
appendicitis  of  any  severity  show  leucocytosis ;  typhoid  almost 
never  does  if  uncomplicated.     Curtis 2  reports  a  case  of  typhoid 
with  a  tumor  and  tenderness  in  the  right  iliac  region  which 
closely  simulated  appendicitis  but  turned  out  to  be  a  floating 
kidney.     The  blood  count  would  have  decided  the  matter. 

3.  Between  appendicitis  and  pus  tube  the  blood  gives  no  help, 
as  both  affect  it  alike. 

4.  Ovarian  or  pelvic  neuralgia  (uncomplicated)  never  causes 
leucocytosis  and  may  be  excluded  by  its  presence.     The  same  is 
true  of  floating  kidney,  which  has  been  sometimes  confounded 
with  appendicitis. 

5.  Gall-stone  colic,  and  renal  colic  if  uncomplicated  by  in- 
flammatory disturbance,  cause  no  leucocytosis,  and  can  there- 
fore  be   distinguished   from   appendicitis  in    most    cases.     If 

1  Medico-Chirurgical  Transactions,  1888,  Ixxi. ,  p.  165. 

2  "Twentieth  Century  Practice  of  Medicine,"  vol.  viii.,  p.  461. 


230  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

cholangitis,  cholecystitis,  pyelitis,  or  severe  cystitis  compli- 
cate the  colic,  the  examination  of  the  blood  will  be  no  help 
to  us. 

6.  Impaction  of f wees  in  the  caecum  will  not  cause  any  leucocy- 
tosis  and  may  be  excluded  when  such  is  present.     The  count 
may  be  of  use,  it  seems  to  me,  in  deciding  us  whether  an  enema 
ought  to  be  given.     It  is  sometimes  desirable  to  give  an  enema 
in  cases  simulating  appendicitis,  to  help  clear  up  the  diagnosis, 
but  some  physicians  are  afraid  to  do  so  for  fear  of  causing  a 
walled-off  abscess  to  break  into  the  general  peritoneal  cavity. 
In  such  cases,  if  no  leucocytosis  were  present,  we  might  go 
ahead  with  a  clearer  conscience. 

Mr.  B—  -  entered  the  Massachusetts  General  Hospital  Sep- 
tember 20th,  1893,  with  a  diagnosis  of  appendicitis.  For  twenty 
days  he  had  been  having  pain  and  tenderness  in  the  region  of 
the  appendix,  pain  being  controlled  by  morphine.  TJie  bowels 
had  been  loose,  he  said.  There  was  dulness,  tenderness,  and  a 
distinct  tumor  in  the  region  of  the  appendix,  with  slight  pyrexia. 
The  blood  count  showed  only  8,000  leucocytes.  He  was  given 
a  compound  cathartic  pill,  had  a  large  movement  of  the  bowels, 
and  all  symptoms  and  signs  disappeared. 

7.  Extra-uterine  pregnancy  and  pelvic  hsematocele  may  cause 
leucocytosis  like  appendicitis,  but  do  not  increase  fibrin  unless 
peritonitis  is  present,  and  are  likely  to  slioiv  a  marked  diminution 
in  red  corpuscles  if  the  hemorrhage  is  severe.     The  red  cells 
are  normal  in  appendicitis  except  in  chronic  cases  with  ab- 
scess. 

8.  Floating  kidney  has  been  already  mentioned  in  Curtis'  case, 
where  in  combination  with  typhoid  it  closely  resembled  appen- 
dicitis.    Even  without  the  presence  of  typhoid,  the  same  dif- 
ficulty of  diagnosis  may  arise  between  appendix  and  floating 
kidney.     The  presence  of  leucocytosis  could  not  be  accounted 
for  by  the  latter. 

One  of  the  next  most  common  forms  of  abscess  seen  in 
medical  wards  is  pyosalpinx,  which  I  shall  call  by  the  English 
name  of  "pus  tube."  As  this  produces  the  same  effect  on  the 
blood  as  pelvic  abscess  or  pelvic  peritonitis,  I  shall  consider  the 
three  processes  together.. 


PUS   TUBE,    PELVIC   ABSCESS,    ETC. 


231 


PUS  TUBE,  PELVIC  ABSCESS,  AND  PELVIC  PERITONITIS. 

Almost  all  that  has  been  said  of  appendicitis  applies  equally 
well  to  these  conditions. 


TABLE  XIX.,  A. — Pus  TUBE  AND  PELVIC  ABSCESS. 


£  ti 

•<     OQ 

•3  VQ 
Q3"<B 

m  o 

J! 

go  9 

O  QjS 

^85 

£•*  «* 

Remarks. 

36    F. 

43,000 

Double  pus  tube;  too  weak  to  operate     December  15th 

31,000 

December  22d 

45,900 

December  29th  ;  abscess  burst  per  vaginam 

20,200 

January   4th   abscess  opened  in  groin 

15,200 

"          8th 

12,200 

"         llth. 

.    F. 

5,400,000 

34,000 

Pelvic  abscess 

38    F. 

34,000 

Pus  tube     June  18th 

34,600 

June  19th. 

35,000 

"     20th 

40,000 

"     27th,  fever  and  vomiting  just  before  catamenia., 

17,300 

July    1st   temperature  normal 

11,500 
12,000 



"      8th,  mass  decreasing. 
"     14th,  slight  thickening  still 

34    F. 
..    F. 

4,202,000 
4,880,000 

32,500 
30,000 

60 

Pus  tube;  septic  arthritis;  jaundice. 
Pus  tube. 

23    F. 
29    F. 

'4,544,000 

29,200 

28,800 



Double  pus  tube. 
General  purulent  peritonitis 

20    F 

27300 

26    F. 

3,800,000 

27,000 
25,000 

65 

Double  pus  tube.    November  17th. 
November  19th,  operated 

43    F. 

5,210  000 

26,600 

Pus  tubes 

28    F. 

5,120,000 

24,400 

Pus  tube. 

..    F. 

24,400 

Pus  tube  four  weeks'  duration 

24    F. 

5  376  000 

24000 

Pus  tube 

3,760,000 

23,000 

Pelvic  abscess  (fetid  pus) 

45    F. 
..    F. 
..    F. 

5,200,'obb' 
5200000 

22.000 
22,000 
22000 

'.".".'.'.'. 

Pus  tube. 
Pus  tube. 
Pus  tube  •  operation  •  pus  found 

35    F. 
19    F. 

3,704,000 

21,100 
20200 

65 

Pus  tube  operated. 
May    1st 

23800 

26    F. 
..    F. 

5,021.000 
4,400,000 

20,000 
19800 



Pus  tube. 
Pus  tube 

21    F. 

19,000 
21,100 



Pus  tube.    Temperature  99°.    April  26th. 
No  fever     May  2cl 

16  000 

May  4th 

54    F. 
25    F. 

3,940,000 
3,860,000 

18,600 
19,600 
21,600 
18,200 
16,300 
19,000 

18,800 

"*60"' 

"    9th. 
No  fever. 
May  18th,  flow  of  pus  from  os  started  by  manipulation. 

Out  doors. 
Pus  tube  and  ovaritis;  operation;  pelvis  full  of   foul 
pus;  recovery  after  hysterectomy. 
Pus  tubes. 

?    F. 

4,592,000 

18  800 

tube 

18    F. 
32    F. 

3,840,000 
5,776.000 

18,500 
18,000 

55 

tube;  three  hours  after  food, 
tubes. 

28    F. 

5,000  000 

18000 

tube 

•30    F. 

3,410  000 

18  000 

tube  etc 

21    F. 

5,088,000 

16  400 

tube;  syphilis     October  7th 

5,184  000 

18000 

October  12th 

22   F. 
..    F. 

4,300,000 
3,800,000 

16,000 
16  000 

80 

Pus  ear. 
Pus  tube 

35    F. 

15  600 

Pus  tube     May  8th 

18  200 

36    F. 
19    F. 

4,656,000 

15,600 
15,300 

60 

Pus  tube  ;  large  amount  of  pus  found. 
Pelvic  peritonitis. 

232 


SPECIAL  PATHOLOGY   OF  THE  BLOOD. 


TABLE  XIX.,  A.— Pus  TUBE  AND  PELVIC  ABSCESS  (Continued), 


!l 

n 

«£ 

JU 
11 

Per  cent 
haemo- 
globin. 

Remarks. 

36    F. 

3,696,000 

14,975 
12  600 

48 

Pus-tube.    July  21st,  chills  and  delirium. 
July  23d 

20   F. 
38    F. 
..    F. 
35    F 

4,310,000 
3,008,000 
4,700,000 

14,800 
13,853 
12,500 
12200 

30 
22 

70 

"     25th;  operated. 
Pus  tube;  chlorosis. 
Pus  tube. 
Pus  tube  (double)  ;  operated. 
Pus  tube;  slight 

21    F 

12  200 

Pus  tube     June  2d 

12300 

June  10th. 

19    F 

3  910  000 

12  000 

Pus  tube 

..    F. 

33    F. 
47    F. 

4,756,000 
4,240,009 

11,850 
13,750 
11,000 
10,600 
11,000 
11  500 

63 
55 

Pus  tube.    January  5th  and  6th. 

Pus  tube.    Not  operated;  very  slight. 
Chronic  salpingitis.    June  21st. 
June  25th,  better. 
"     29th. 

21    F. 

3,800,000 
7,000,000 

10,400 
10,000 

64 

Pelvic  peritonitis. 
Pelvic  abscess  (?). 

38   F. 

4,125,000 

10,000 
17  000 

60 

Pelvic  abscess.    August  28th. 
September  3d  temperature  up 

13,400 

"           6th,  normal  temperature. 

24    F. 

9,000 
9,200 



Salpingitis,  9  A.M.  ;  99.4°. 
4  •  15  P.  M.  ;  five  days  in  hospital. 

23    F 

472000 

7,500 

Pus  tubes  (small;  size  of  finger). 

..    F. 

5,840,000 

7,200 

Pus  tube. 

From  these  data  together  with  nineteen  otner  counts  not 
here  recorded  I  conclude  that :  Increasing  counts  of  leucocytes 
usually  point  to  the  need  of  an  operation ;  stationary  leucocy- 
tosis  to  a  well  walled-off  abscess.  The  size  of  the  count  is  a 
rough  measure  of  the  size  of  the  abscess,  and  cases  ivithout 
leucocytosis  rarely  need  operation  and  usually  recover  under 
palliative  treatment,  as  also  do  many  with  leucocytosis. 

Differential  Diagnosis. 

Pelvic  pain  and  soreness  may  be  as  great  in  various  non- 
suppurative  conditions  (ovarian  neuralgia,  etc.)  as  when 
abscess  is  present,  but  the  leucocyte  count  is  raised  in  none  of 
the  pelvic  disorders  of  women  except  abscess,  septicaemia  (puer- 
peral, after  abortion,  etc.),  and  hemorrhage  (menorrhagia, 
metrorrhagia,  ruptured  tubal  pregnancy).  Endometritis  and 
cystitis  usually  cause  no  leucocytosis.  The  application  of  these 
rules  will  not  infrequently  help  in  the  diagnosis  of  pelvic  disease 
and  in  deciding  how  much  importance  to  attach  to  the  com- 
plaints of  pain,  tenderness,  etc.,  in  a  doubtful  case.  The  ab- 


OTITIS   MEDIA. 


233 


sence  of  leucocytosis  makes  us  rightly  confident  that  no  abscess 
of  any  considerable  size  exists. 


OTITIS  MEDIA. 

Most  cases,  if  purulent,  show  leucocytosis  both  before  and 
after  paracentesis.  If  serous  (see  Table  XIX.,  B,  cases  5,  10, 
11,  12)  the  count  is  usually  lower,  and  we  can  predict  with 
moderate  certainty  whether  serum  or  pus  will  be  found  on 
puncturing  the  drum.  When  the  mastoid  is  involved  the  count 
runs  higher.  If  the  case  drags  on,  the  haemoglobin  may  get 
low,  otherwise  the  red  cells  are  not  affected. 

In  some  cases  the  blood  alone  enables  us  to  distinguish  otitis 
and  its  effects  from  typhoid.  In  a  case  recently  examined 
which  several  excellent  clinicians  pronounced  typhoid,  though 
there  was  a  marked  leucocytosis  and  no  serum  reaction,  the 
autopsy  showed  pus  in  the  jugular  and  lateral  sinus  but  no 
typhoid. 

TABLE  XIX.,  B.— OTITIS  MEDIA. 


£ 

Age. 

X 

i 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

i 

6 

F. 

36,  700 

Nephritis  acuta.     April  30tli. 

27,300 

May    7th. 

34,400 

May  14th,  otitis  only. 

27,000 

May  22d. 

21,000 

May  28th,  slight;  discharge  still. 

2 

2 

M. 

23,000 

55 

3 

6 

M 

18,600 

20 

4 

45 

M. 

14,500 

With  cerebral  abscess. 

5 

Adult. 

M. 

4,786,000 

16,800 

Serous. 

0 

47 

F. 

4,168,000 

16,600 

65 

Double  purulent  ;  vent  not  free  ; 

mastoid  sore. 

7 

19 

F. 

5,120,000 

16,480 

88 

April  28th. 

8,800 

49 

May  5th,  well. 

8 

Adult. 

F. 

5,942,000 

15,200 

Pus. 

9 

Adult. 

F. 

4.472,000 

14,750 

60 

December  7th,  hysteria. 

5,416,000 

9,750 

46 

December  25th  (during  dyspnceic 

•ind  cyanotic  attack). 

10 

27 

F. 

4,850,000 

8,500 

69 

Serous. 

11 

7 

F. 

4,416,000 

6,400 

Catarrhal. 

12 

Adult. 

F. 

4,100,000 

4,000 

Serous. 

13 

4 

M. 

Marked 

Purulent  ;     chronic    right,     acute 

leuco- 

left.    Diff.  116  cells  ;    polymor- 

cytosis. 

phonuclear  cells,    57  per  cent  ; 

lymphocytes,  31  ;  eosinophiles,  3. 

234  SPECIAL    PATHOLOGY    OF    THE   BLOOD. 

OSTEOMYELITIS. 

In  four  cases  in  which  no  external  opening  was  present,  the 
patient  complaining  only  of  pajn  in  the  bone,  the  counts  of  leu- 
cocytes were  29,600,  25,600,  24,310,  and  18,000;  in  each  the 
prediction  that  pus  would  be  found  was  verified  at  operation. 
Three  differential  counts  in  chronic  cases  with  sinuses  showed 
nothing  remarkable,  no  increase  of  eosinophiles  and  no  mye- 
locytes. 

The  diagnostic  value  of  the  blood  in  osteomyelitis  seems  to 
me  considerable,  inasmuch  as  it  is  difficult  by  the  symptoms 
alone  to  feel  sure  enough  of  the  existence  of  pus  to  be  willing  to 
operate.  "Rheumatic  pains,"  "growing  pains,"  and  neuralgia 
can  »be  excluded  by  the  presence  of  leucocy tosis. 

OTHEE  ABSCESSES. 

(1)  Felon. — It  is  striking  to  see  how  small  a  collection  of 
pus  can  raise  the  leucocyte  count.     Felons  containing  less  than 
one-half  drachm  of  pus  may  have  a  leucocytosis  of  15,000  to 
22,000.     I  have  counted  the  blood  in  three  such  cases.     The  ele- 
ment of  septicaemia  must  be  considerable.     It  seems  to  make 
no  difference  whether  or  not  the  pus  is  under  great  tension.     The 
leucocyte  count  does  not  fall  sharply  after  the  felon  is  opened, 
but  gradually  diminishes  during  the  next  seven  to  ten  days. 
Even  a 

(2)  Gum  boil  raised  the  white  cells  to  27,000  in  one  case.     An 

(3)  Abscess  of  the  vulva  showed  23,500  leucocytes  per  cubic 
millimetre,  and  an 

(4)  Abscess  of  the  vagina,  12,800.     Other  varieties  are: 

(5)  Parotid  abscess,  45,500  leucocytes  per  cubic  millimetre. 

(6)  Subpectoral  abscess,  16,000   leucocytes   per  cubic  milli- 
metre. 

(7)  Abscess  of  the  neck,  22,200  leucocytes  per  cubic  milli- 
metre.    Carbuncle,  41,000  leucocytes  per  cubic  millimetre. 

(8)  Psoas  abscess  (infected),  50,000  leucocytes  per  cubic  mil- 
limetre. 

(9)  Abscess  of  ovary,  26,000  leucocytes  per  cubic  millimetre. 

(10)  One  case  of  perinephritic  abscess  was  watched  for  some 
days  while  the  patient  was  getting  up  strength  for  an  operation. 
It  was  an  abscess  of  several  months'  standing,  not  increasing  in 


OSTEOMYELITIS. 


235 


size  during  the  last  mouth,  and  the  counts,  as  we  should  expect, 
did  not  rise  or  fall  considerably  but  showed  a  steady  well-marked 
leucocytosis. 

July  29th,  white  cells,  21,400 

"     30th,       "         "     21,200 

August    8th,      "         «     22,400 

llth,      "         "     23,000 

"       24th,      «         «     22,200.     (Operation.) 

A  second  case  counted  only  showed  16,000.  Both  abscesses 
contained  over  a  quart  of  pus. 

A  third  case,  evidently  tubercular  in  origin  and  probably  not 
much  infected  with  pyogenic  cocci,  showed  only  10,000  white 
cells  per  cubic  millimetre. 

(11)  Abscess  of  the  Lung. — Five  cases  following  pneumonia 
have  occurred  at  the  Massachusetts  Hospital  within  the  last 
three  years;  the  counts  are  as  follows:  Case  I.,  16,800;  Case 
II.,   16,000;    Case  III.,   16,400;   Case  IV.,   30,000;    Case  V., 
5,100. 

(12)  Subphrenic  abscess,  four  cases. 


Case. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

Remarks. 

1 
2 

4,450,000 

53,267 
25  600 

May  16th 

3 
4 

3,200,000 

15,500 
17,600 
22,000 
15,300 

"SS" 

38 

May  17th. 
May  20th. 

October  20th.     Supposed  typhoid 

13,800 

for  first  week. 
October  23d. 

16,600 

October  27th. 

18,000 

November  5th. 

22,500 



November   10th.      Operation  ;    a 
quart  of  pus  ;  recovery. 

Diagnostic  Value. 

1.  The  case  of  vulvar  abscess  was  so  morbidly  modest  that 
she  complained  of  all  parts  of  her  body  except  the  one  diseased 
and  gave  a  train  of  symptoms  which  utterly  failed  to  account 
for  the  leuaocytosis.  The  presence  of  this  leucocytosis  called 
for  a  much  more  searching  physical  examination  than  would 
have  otherwise  been  made,  and  the  seat  of  real  trouble  was  dis- 
covered. 


236  SPECIAL    PATHOLOGY    OF    THE   BLOOD. 

2.  (a)  The  diagnosis  between  perinephritic  abscess  and  cyst 
of  the  kidney  is  materially  assisted  by  the  fact  that  the  former 
causes  leucocytosis,  while  the  latter  (see  page  305)  does  not. 

(b)  Both  cancer  of    the  kidney  and  perinephritic    abscess 
cause  leucocytosis,  but  if  fibrin  is  not  increased  cancer  is  the 
more  likely  of  the  two.     This  differential  mark  has  served  me 
well  in  two  cases. 

(c)  Hydatid  of  the  kidney  and  pyonephrosis  are  not  to  be 
distinguished  from  perinephritic  abscess  by  the  blood  examina- 
tion.    In  abscess  of  the  lung  the  blood  gives  no  information 
that  cannot  be  more  easily  gained  in  other  ways. 

3.  Subphrenic  abscess  may  be  confounded  with  malignant 
disease,  both  of  which  may  cause  leucocytosis ;  but  the  absence 
of  any  increase  of  fibrin  speaks  against  the  existence  of  an  ab- 
scess. 

GONORRHCEA. 

The  red  cells  are  not  affected,  but  in  acute  cases  a  moderate 
leucocytosis  is  present  and  fibrin  is  increased.  Qualitatively, 
the  white  cells  have  been  said  by  Neusser  and  others  to  show  an 
increased  percentage  of  eosinophiles  corresponding  to  the  large 
proportion  of  these  cells  in  the  urethral  discharge,  but  Yorbach 
has  carefully  studied  twenty  cases  with  reference  to  this  point 
and  finds  the  eosinophiles  in  the  blood  to  vary  from  0.5  to 
11.5  per  cent — averaging  4.2  per  cent — within  normal  limits. 

YELLOW  FEVER. 

Jones  l  found  coagulation  slow,  the  red  cells  not  much  dimin- 
ished but  showing  decided  degenerative  changes;  hsemoglobi- 
nsemia  is  common.  He  makes  no  observations  as  to  the  white 
corpuscles.  Pothier  of  New  Orleans,  studying  the  epidemic  of 
1897,  found  the  following:  "Never  less  than  4,500,000  red  cells 
per  cubic  millimetre,  an  average  of  8,000-10,000  leucocytes. 
The  haemoglobin,  on  the  other  hand,  was  never  over  80  per 
cent,  and  in  some  cases  as  low  as  60  per  cent.  Neither  fresh 
nor  stained  specimens  showed  anything  abnormal  about  the 
corpuscles." 

A  case  recently  observed  at  the  Massachusetts  Hospital 
showed  two  days  before  death  7,800  leucocytes,  92  per  cent  of 
1  Journal  of  the  American  Medical  Association,  March  16th,  1895. 


TYPHUS   FEVER. 


237 


haemoglobin,  with  an  absence  of  the  typhoid  serum  reaction. 
Through  the  kindness  of  Dr.  Pothier  I  have  been  able  to  study 
cover  slips  from  twelve  cases  of  yellow  fever  from  the  Charity 
Hospital  of  New  Orleans.  The  differential  counts  of  leuco- 
cytes are  as  follows : 


i. 

II. 

III. 

IV. 

V. 

VI. 

VII. 

VIII. 

IX. 

X. 

XI. 

XII. 

Polymorphonuclear     n  e  u  t  r  o  - 
philes         

77 

74 

Pft 

86 

87 

88 

97 

84 

86 

81 

77 

73 

Small  lymphocytes  

18 
5 

22 
v 

15 
2 

11 
2 

8 
5 

4 

R 

3 

5 
11 

4 
10 

6 
6 

4 

18 

20 
6 

Eosinophiles                    

•9, 

5 

1 

1 

5 

4 

Ked  cells  showed  nothing  except  in  Case  VIII.,  where  there 
were  marked  deformities  and  a  few  normoblasts.  In  some  cases 
there  was  a  marked  leucocytosis,  in  others  none.  (For  serum 
reactions,  see  page  425) . 


TYPHUS  FEVER. 


Ewing  '  in  four  cases  found  no  leucocytosis. 
no  leucocytosis,  as  the  following  case  shows : 


Tumas 2  found 


Date. 

Day  of 

disease. 

Temperature. 

Bed  cells. 

Per  cent 
haemoglobin. 

White  cells. 

A.M. 

P.M. 

January    4th  

4th. 

40.0 

5th  

5th. 

39.2 

39.6 

4,440,000 

80 

9,600 

6th  

6th. 

39.0 

39.5 

4,220,000 

77 

4,800 

7th  

7th. 

39.0 

40.0 

8th  

8th. 

39.2 

39.3 

4,280,000 

v77 

3,200 

9th  

9th. 

39.0 

39.5 

10th  

10th. 

38.8 

39.2 

4,440,000 

77 

3,200 

llth  

llth. 

38.3 

39.3 

12th  

12th. 

39.0 

39.2 

4,380,000 

80 

1,600 

13th  

13th. 

38.8 

39.5 

4,780,000 

80 

3,200 

14th  

14th. 

38.7 

39.0 

15th  

15th. 

38.0 

38.7 

4,960,000 

80 

1,600 

16th  

16th. 

38.1 

38.8 

17th  

17th. 

38.7 

38.6 

4,160,000 

70 

4,800 

18th  

18th. 

37.7 

38.2 

19th  

19th. 

36.6 

38.5 

3,820,000 

67 

1,600 

20th  

20th. 

38.1 

38.3 

21st  

21st. 

37.5 

38.1 

3,450,000 

62 

8,280 

22d  

22d. 

38.1 

37.8 

3,450,000 

60 

3,200 

23d 

23d 

37  5 

38  0 

24th  

24th. 

37.4 

38!o 

3,130,000 

50 

3,200 

25th  

25th. 

37.4 

39.3 

"        26th 

26th. 

39.2 

Died  on  the  26th. 

1  Ewing  :  New  York  Medical  Journal,  December  16th,  1893. 

2  Arch.  f.  klin.  Med.,  vol.  41,  p.  363. 


238  SPECIAL    PATHOLOGY   OF   THE   BLOOD 

On  the  other  hand,  Everard  and  Demoor, l  and  "Wilks 2  found 
leucocytosis. 

MALTA  FEVER. 

According  to  the  article  in  Allbutt's  recent  "  Text-book  of 
Medicine"  the  red  cells  fall  gradually  in  the  course  of  the  fever 
from  5,000,000  to  about  3,500,000.  Bruce  finds  the  leucocytes 
normal  in  most  cases.  (See  also  page  424.) 

RELAPSING   FEVER. 
(See  Blood  Parasites,  page  425). 

GLANDERS. 

Christol  and  Kiener  (Comptes  Rendus  de  T 'Acad.  des  Sciences, 
November  23d,  1868)  reported  leucocytosis  in  glanders.  In  a 
fatal  case  of  acute  glanders  with  autopsy  which  was  recently 
studied  at  the  Massachusetts  Hospital  the  following  counts  were 
recorded : 

October  24th,  1897.     Leucocytes,  13,600  ;  hsemoglobin,  100  per  cent. 

October  31st,   1897.     Leucocytes,  11,600. 

November    4th,  1897.     Leucocytes,  13,000. 

November    9th,  1897.     Leucocytes,  12,600. 

November  12th,  1897.     Leucocytes,  12, 400. 

Serum  reaction  absent ;  fibrin  increased ;  pure  culture  of  glanders 
bacilli  from  abscesses ;  86  per  cent  of  the  leucocytes  were  polymorpho- 
nuclear ;  eosinophiles  absent. 

The  bacilli  of  glanders  can  occasionally  be  cultivated  from 
the  blood. 

THE   BUBONIC   PLAGUE. 

In  1895  Aoyoma,  a  Japanese  observer,  studied  the  blood  of 
this  disease.3  He  found  the  bacilli  peculiar  to  the  disease  by 
cover-slip  preparations  from  the  blood.  The  red  corpuscles  were 
not  altered  except  that  their  number  per  cubic  millimetre  was  at 
times  increased  (e.g.,  7,600,000,  8,190,000).  The  cause  of  this 
I  do  not  know,  but  it  accounts  for  part  of  the  leucocytosis.  The 

1  Annales  de  1'Institut  Pasteur,  February,  1893. 

2  Ref.  in  Sajous'  Annual,  1895. 

3 "  Mittheilungen  aus  d.  Med.  Fac.  d.  Kaiserlich  Japanischen  Uni- 
versitat,"  vol.  iii.,  No.  2.  Tokyo,  Japan,  1895. 


TRICHINOSIS. 


230 


white  corpuscles  showed  a  marked  increase — 20,000  to  200,000  ( !) 
per  cubic  millimetre.  This  leucocytosis  was  made  up  almost 
wholly  of  polymorphonuclear  leucocytes ;  the  eosinophiles  were 
markedly  diminished,  and  the  blood  plates  were  increased. 

ACTINOMYCOSIS. 

Ewing  (loc.  cit.)  reports  leucocytosis  (21,500)  in  a  single  case. 
In  a  case  of  actinomycosis  of  the  liver  (autopsy)  which  oc- 
curred at  the  Massachusetts  General  Hospital  in  1897  the  fol- 
lowing counts  were  recorded : 

June  18th,  leucocytes : 31, 700 

June  19th,  leucocytes 28,400 

June  25th,  leucocytes 28,200 


TRICHINOSIS. 

At  the  International  Medical  Congress  at  Moscow  (1897) 
Thayer  reported  two  cases  of  trichinosis  in  both  of  which 
trichinae  were  demonstrated  in  the  muscle.  The  blood  was  of 
the  greatest  interest.  Both  cases  showed  an  enormous  relative 
and  absolute  increase  of  eosinophiles  as  the  following  counts 
show: 


Cas 

el. 

Case  II. 

Red  cells  

March  8th,  1896. 
4,232,000 

April  28th,  1896. 

5,  000,  000 

White  cells 

16  500 

17  000 

13  000 

Polymorphonuclear     neu- 
trophiles  ' 

50  per  cent 

6  6  per  cent 

37  per  cent 

Small  lymphocytes  . 

5 

19  5 

11 

Large  lymphocytes  
Eosinophiles  

7 
38       " 

5.2 
68.2(1)   " 

5 

44 

In  the  second  case  it  was  the  blood  examination  that  sug- 
gested the  diagnosis,  the  symptoms  being  rather  those  of 
typhoid  or  malaria. 

I  have  recently  had  a  case  strongly  resembling  these.  In  a 
patient  .who  had  just  returned  from  Germany  where  he  had 
suffered  from  a  severe  gastro-intestinal  attack,  tender  spots  ap- 
peared in  various  muscles,  and  swelling  of  the  face  and  hands, 
weakness,  and  anaemia  were  present.  His  blood  showed : 


240  SPECIAL  PATHOLOGY   OF  THE  BLOOD. 

September  November 

30th,  1897.  4th,  1897. 

Red  cells 5,120,000  4,900,000 

White  cells 11,000  7,000 

Per  cent.  Per  cent. 

Polymorphonuclear  neutrophiles           39  36.5 

Small  lymphocytes 28  38 

Large  lymphocytes 3  8 

Eosinophiles 28  17 

Basophiles  ("mastcellen") 2  .5 

This  patient  is  unwilling  to  have  a  bit  of  muscle  excised  so 
that  the  diagnosis  of  trichinosis,  which  I  regard  as  probable, 
cannot  be  verified.  He  is  recovering  rapidly. 

EPIDEMIC  DROPSY. 
(Acute  Anaemic  Dropsy.) 

MacLeod  in  Vol.  III.  of  Albutt's  "System  of  Medicine" 
describes  under  this  title  a  disease  not  uncommon  in  India  and 
other  tropical  countries.  The  blood  shows  a  marked  and  con- 


FIG.  35.— Blood  in  Epidemic  Dropsy.     Note  oval  shape  of  corpuscles.    Magnified  350 

diameters. 

stant  anaemia  with  leucocytosis  and  an  "  increase  of  granular  or 


BERI-BERI.  241 

molecular  matter  in  the  serum."  Dr.  Greene,  of  the  United 
States  Marine  Hospital  service,  recently  wrote  me  an  account  of 
two  cases  strongly  resembling  MacLeod's  description  of  epi- 
demic dropsy ;  these  cases  were  observed  by  Dr.  Greene  at  Key 
West,  Florida.  One  was  fatal  and  the  other  recovered.  The 
blood  of  both  cases  was  notable  in  that  the  corpuscles  were 
almost  invariably  oval  instead  of  round,  reminding  him  of  the 
blood  of  amphibia.  He  was  good  enough  to  send  me  prepara- 
tions of  the  blood;  a  microphotograph  of  one  of  them  is  here 
reproduced.  Rouleaux  formation  was  absent,  another  point  in 
common  with  amphibian  blood.  There  was  no  apparent  in- 
crease of  the  leucocytes  when  I  saw  the  blood,  late  the  conva- 
lescence of  the  second  case.  (On  the  significance  of  oval  forms, 
see  page  87;) 

TETANUS. 

In  a  single  (fatal)  case  of  tetanus  treated  with  antitoxin  I  ob- 
served the  following  counts : 

White  cells.  Haemoglobin. 

June  21st,  1897 11,100  70  per  cent. 

June  23d,  1897 11,900 

The  eosinophiles  do  not  decrease  as  in  most  fevers. 

BERI-BERI. 

In  a  single  afebrile  case  seen  at  the  Massachusetts  Hospital 
the  following  is  recorded:  Eed  cells,  3,896,000;  white  cells, 
7,800;  haemoglobin,  48  per  cent. 

The  eosinophiles  are  said  to  be  much  increased  in  the  acute 
stages.     Spencer  (Lancet,  January  2d,  1897)  states  that  there  is 
no  leucocytosis. 
16 


CHAPTER  V. 

DISEASES  AFFECTING  THE  SEROUS  MEMBRANE. 

1.  SEROUS  effusions,  representing  probably  a  milder  type  of 
infection  than  purulent  effusions,  have  less  effect  than  the  latter 
upon  the  blood. 

2.  The  serous  effusions,  however,  must  be  subdivided  into 
the  tubercular  and  the  non-tubercular.     The  former,  like  most 
forms  of  tuberculosis  (see  page  255),  rarely  raise  the  leucocyte 
count,  while  the  latter  may  do  so,  though  in  a  lesser  degree  than 
purulent  processes. 

Tubercular  affections  of  serous  membranes  have  been  dealt 
with  elsewhere  (page  264) ;  but  an  exception  was  then  made  of 
pleurisy,  for  although  there  is  reason  to  believe  that  the  majority 
of  cases  of  serous  pleurisy  are  due  to  tuberculosis,  we  rarely 
have  proof  of  it,  and  most  observations  upon  the  blood  of  pleu- 
risy have  not  been  accompanied  by  bacteriological  examination 
of  the  effusion.  Tubercular  cases  have  not  been  distinguished 
from  non-tubercular.  Hence  the  two  are  necessarily  considered 
together  here. 

SEROUS  PLEURISY. 

Von  Limbeck  finds  in  non-tubercular  cases  from  13,000  to 
15,000  leucocytes  per  cubic  millimetre.  The  red  cells  and  hse- 
moglobin  are  not  much  affected  except  in  chronic  cases. 

Bieder  finds  in  non-tubercular  cases  during  the  stage  of  fever 
moderate  leucocytosis,  13,000  in  one  case  in  which  the  bacterio- 
logical examination  showed  the  presence  of  Fraenkel's  diplococ- 
cus  in  the  exudation.  After  the  fever  has  subsided  the  leucocy- 
tosis falls  to,  or  nearly  to  normal,  so  that  cases  examined  for  the 
first  time  some  weeks  after  onset  would  show  no  increase  at  all. 
This  he  thinks  explains  the  results  of  Halla  and  others  who 
found  no  leucocytosis  in  serous  pleurisy.  According  to  Rieder 
the  presence  or  absence  of  leucocytosis  depends  not  so  much 


SEROUS   PLEURISY.  243 

on  whether  the  product  is  serum  or  pus  as  on  whether  the 
trouble  is  stationary  or  advancing. 

In  tubercular  pleurisy  despite  fever  Eieder  found  but  4,600 
white  cells  in  one  case,  and  Pick  got  similar  results  in  two 
cases. 

Hayem  makes  no  clear  distinction  of  tubercular  and  non- 
tubercular  cases  and  states  that  "acute  inflammatory"  pleurisy 
has  from  7,500  to  12,000  leucocytes  per  cubic  millimetre. 
The  fibrin  network  is  much  less  dense  than  in  pneumonia; 
in  most  of  the  tubercular  cases  it  is  not  increased  at  all. 

In  ninety -nine  cases  examined  at  the  Massachusetts  General 
Hospital  the  average  count  of  leucocytes  was  6,130. 

TABLE  XX. —PLEURITIC  EFFUSION  (SEROUS). 

Between    3, 000  and    4,000 3  cases. 

4,000    "       5,000 5  " 

5,000    "       6,000 14  " 

6,000    "       7,000 17  " 

7,000    "       8,000 10  " 

"          8,000    "       9,000 13  " 

9,000    "     10,000 14  " 

10,000    "     11,000 9  " 

11,000    "     12,000 4  " 

12,000    "     15,000 7  " 

Over  15, 000 , 3  " 

Total 99      " 

Average 6,130. 

Here  tubercular  and  non-tubercular  cases  are  not  distin- 
guished, and  a  majority  of  them  were  not  seen  till  the  trouble 
had  been  going  on  two  or  three  weeks.  The  patients  did  not 
seek  advice  until  the  effusion  was  large  enough  to  cause  dysp- 
noea. Of  the  ninety-nine  cases  all  but  fourteen  had  no  leuco- 
cytosis.  Most  of  the  cases  were  afebrile  or  nearly  so,  and  very 
likely  tubercular,  but  no  cultures  were  taken  in  any.  Eight 
cases  reacted  to  injections  of  tuberculin.  None  of  these  eight 
had  leucocytosis. 

The  cases  ivitli  leucocytosis  were  mostly  those  seen  in  the 
febrile  stage,  near  the  beginning  of  the  sickness.  No  differen- 
tial counts  were  made. 

In  chronic  cases  the  red  cells  are  said  to  be  considerably 
diminished,  but  this  has  not  been  the  case  in  our  series:  no 


244 


SPECIAL    PATHOLOGY    OF    THE   BLOOD. 


count  of  under  4, 000, 000  was  recorded,    and  the  coloring  matter 
was  not  much  diminished. 

Summary. 

1.  Red  cells  and  haemoglobin  show  no  important  changes. 

2.  White  cells  not  increased  in  most  cases  except  in  febrile 
stages,  and  not  often  over  13,000  then.     Tubercular  cases  if  un- 
complicated probably  never  have  leucocytosis. 

Diagnostic  Value. 

The  blood  count  may  help  a  good  deal  in  doubtful  cases  by 
excluding  empyema,  pneumonia,  and  malignant  disease  of  the 
lung,  all  of  which  are  accompanied  by  higher  leucocyte  counts. 
Compare  the  average  count  in  serous  pleurisy,  6,130,  with  the 
average  in  pneumonia,  24,000,  or  in  empyema,  18,300.  The  few 
counts  I  have  seen  of  malignant  disease  of  the  lung  have  been 
still  higher. 

Hayem  insists,  rightly  it  seems  to  me,  that  clinicians  could 
get  real  help  from  blood  examination  in  almost  every  case  of 
doubtful  diagnosis  in  which  the  lung  and  pleura  are  in  question. 
In  children  the  leucocytes  are  considerably  increased  by  even  a 
serous  inflammation,  their  blood  reacting  always  more  strongly 
than  that  of  adults  to  any  morbid  influence,  and  in  them  it 
may  be  impossible  to  distinguish  serous  from  purulent  pleu- 
risv. 


PURULENT  PLEURISY    (EMPYEMA). 

The  counts  in  nineteen  cases  observed  at  the  Massachusetts 
Hospital  are  as  follows : 


Case. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

2 

5,440,000 

49,200 
41  500 

51 
60 

8 

35  200 

4 
5 

6,000,000 

32,000 

22,  800 

45 

6 

22,600 

Pneumococcus. 

PERITONITIS. 


245 


Case. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

7 

.8 

9 

10 
11 
12 
13 
14 
15 
16 
17 
18 
19 

22,800 
34,  700 
29,800 
17,700 
22,000 
22,  100 
21,800 
17,200 
27,300 
30,  100 
25,800 
20,600 
14,700 
11,400 
11,700 
18,000 
26,000 

10,800 
18,500 

14,  500 
18,300 
10,000 
16,200 
15,500 
15,200 
14,000 
12,650 
12,450 
12,000 
11,700 
10,900 
7,600 



June  5th. 
June  7th. 
June  8th.     Tapped  turbid  serum. 
June  9th. 
June  10th. 
June  12th. 
June  14th. 
June  22d. 
June  24th. 
June  29th. 
July  8th. 
January  5th. 
January  7th. 
January  23d. 
January  26th.     Tapped. 
January  30th.     Re-accumulation. 
February   3d.      Operated;     pneumo- 
cocoi  and  streptococci. 
December  20th. 
December  22d.    Broke  into  lung  ;  cul- 
ture sterile. 
January  2d. 
January  4th. 
January  9th. 
Pneumococcus. 

Culture  sterile. 

Operated,;  several  pints  of  pus  ;  strep- 
tooocciV 



4,192,000 

48 

"56" 

85 
60 

44 

4,500,000 
4,850,000 

4',  606,'  666 

This  is  in  marked  contrast  with  serous  pleurisy  as  above 
noted.  Yon  Limbeck  noticed  the  same  thing. 

PERITONITIS. 

A  patient  with  serous  pleurisy  (non-tubercular)  is  hardly 
ever  in  danger,  while  if  the  general  peritoneal  cavity  is  the  seat 
of  a  like  inflammation,  recovery  is  almost  out  of  the  question. 

This  clinical  difference  is  parallel  to  the  difference  in  the 
blood  condition.  Any  inflammation  of  the  peritoneum  (non- 
tubercular),  whether  serous  or  purulent,  calls  very  large  numbers 
of  leucocytes  into  the  peripheral  blood.  The  only  exceptions 
to  this  rule  are  those  cases  in  wrhich  the  organism  is  so  over- 
whelmed by  the  disease  that  it  offers  no  resistance.  We  have 


246 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


seen  that  this  same  effect  is  produced  in  the  severest  cases  of 
pneumonia  and  diphtheria,  and  presumably  it  is  true  of  many 
other  infectious  diseases  in  which  the  blood  has  been  less  care- 
fully studied. 

Almost  all  cases  of  general  septic  peritonitis  show  very 
marked  leucocytosis,  and  the  spreading  of  a  localized  process  is 
always  indicated  by  an  increasing  leucocytosis.  But  here  and 
there  it^happens  that  the  patient  cannot  react  against  the  disease 
at  all,  and  then  the  leucocytes  are  normal  or  diminished.  This 
never  occurs  in  empyema  because  the  system  is  never  so  over- 
whelmed by  a  septic  process  in  the  pleura.  The  fibrin  network 
is  increased  in  almost  all  cases.  The  following  counts,  all  in 
fatal  cases,  illustrate  these  points : 

TABLE  XXI. — GENERAL  PERITONITIS. 


No. 

Age. 

Sex. 

Bed  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 
2 

3 
4 
*i 

34 
Adult. 

27 
Adult. 
31 

F. 

F. 

M. 
F. 
M 

4,860,000 
7,000,000 

5,317,000 
4,000,000 

54,000 
32,000 

24,000 
22,000 
19000 

75 

Abscess  of  spleen  (?). 
Purulent;  from  appendix  —  myelocytes, 
2  per  cent. 
Dysentery,  with  perforation. 
Chronic,  purulent. 
Ruptured  bladder 

6 

7 
8 

9 
10 
11 

Adult. 
Adult. 
52 

Adult. 
41 

M. 
M. 
F. 

M. 

F. 

6,000,000 

5,760,000 
6,840,000 

16,000 
6,000 
5,328 

5,300 
4,600 
Marked 

"95" 

Moribund. 
Purulent;  operation.     Death. 
Obstruction:    died  in  three  days;    au- 
topsy. 
Purulent.     Death  within  24  hours. 
"       24       " 
After  appendix   operation     Diff    1  000 

19 

21 

M. 

increase. 

45,200 

cells:    Polymorphonuclear  cells,  90.5 
per  cent;   lymphocytes,   9.5;   eosino- 
philes,  0;  myelocytes,  1. 
June  30th 

1? 

38 

F 

9,000 
1  700  ' 



July  2d.     Autopsy. 

2,100! 



August  3d. 

Diagnostic  Value. 

1.  When  a  diagnosis  rests  between  peritonitis  and  (a)  ob- 
struction (non-malignant);  (6)  malignant  disease;  (c)  hysteria, 
phantom  tumors  or  malingering,  the  presence  of  marked  leuco- 
cytosis with  increase  of  the  fibrin  network  speaks  strongly  in 
favor  of  peritonitis. 

Obstruction  or  malignant  disease  may  increase  the  number 
of  leucocytes,  but  rarely  increases  the  amount  of  fibrin. 

Hysterical  or  malingering  patients  have  normal  blood. 


PERICARDITIS. 


247 


2.  We  cannot  distinguish  serous  from  purulent  peritonitis 
in  septic  cases,  but  tubercular  peritonitis  can  always  be  excluded 
if  leucocytosis  is  present. 

3.  As  to  the  "chronic  granular  peritonitis,"  non-tubercular 
and  non-septic,  I  have  seen  no  reference  in  hsematological  litera- 
ture and  have  no  first-hand  knowledge. 

4.  In  the  ivorst  cases  leucocytosis  may  be  absent,  as  in  the 
most  virulent  type  of  pneumonia. 

PERICARDITIS    (WITH  EFFUSION). 

As  in  most  other  inflammations  of  serous  membranes  we  can 
distinguish  the  tubercular  cases  which  have  no  leucocytosis 
from  the  rheumatic  or  septic  cases  which  always  increase  the 
white  cells.  The  tubercular  cases  are  discussed  under  tuber- 
culosis (see  page  267).  The  following  counts  illustrate  the 
rheumatic  form  of  the  disease : 


Case. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

42  400 

November    3d,  1895 

32  600 

November    7th,  1895. 

19  200 

November  llth,  1895. 

17,  500 

December    8th   effusion  nearly  gone 

2 

2,632,000 

21,600 

27,100 

45 

December    24th,   endo  -  pericarditis, 
chronic  nephritis, 
December  26th 

36,600 
26,  700 
19,200 

December  29th,  no  fever. 
May  1st. 
May  3d. 

24,800 

May  4th. 

28,600 

May  7th. 

20,  100 

May  8th 

3 

4,568,000 

26,000 
19,400 

67 

December  14th. 
December  20th,  effusion  subsiding. 

4 

24,  000 

5 
6 

4,168,000 

19,447 
15  400 

67 

7 
8 



14,600 
12,000 

65 
63 

Autopsy. 
Tapped. 

Hay  em  has  noted  that  pericarditis  is  far  more  apt  to  pro- 
duce leucocytosis  than  is  endocarditis. 

Diagnostic  Value. 

In  excluding  cardiac  hypertrophy  or  simple  dilatation  with 
ruptured  compensation,  both  of  which  may  occasionally  simulate 


248 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


a  pericardial  effusion,  the  presence  of  marked  leucocytosis  is 
absolutely  decisive.  When  we  are  sure  that  effusion  exists,  the 
absence  of  leucocytosis  points  strongly  to  a  tubercular  process 
as  its  cause. 

MENINGITIS. 

Leucocytosis  is  usually  well  marked.    Von  Limbeck  considers 
that  tubercular  meningitis  can  be  distinguished  from  purulent 
by  the  absence  of  leucocytosis  in  tubercular  cases,  but  Osier  ' 
states  that  many  cases  of  tubercular  meningitis  do  have  leucocy- 
tosis throughout  their  course,  and  my  own  observations  in  seven? 
cases  tend  to  confirm  this.     Of  Eieder's  cases,  one  had  leucocy- 
tosis and  one  did  not.     Zappert's  case  had  11,130  white  cells, 
and  Ziemke  one  with  17,500.     It  seems,  therefore,  that  we  some- 
times have  here  an  exception  to  the  rule  that  tubercular  proc- 
esses do  not  produce  leucocytosis.      Certainly  some  cases  do 
follow  this  rule.     But  however  this  may  be,  it  is  certain  that 
purulent  meningitis,  whether  secondary  or  of  unknown  origin, 
is  characterized  by  high  leucocyte  counts  (Table  XXII.),  and 
if  in  a  case  evidently  of  meningitis  of  some  kind  leucocytosis 
is  absent,  the  case  is  probably  tubercular  in  origin. 

TABLE  XXII.  —MENINGITIS. 


No. 

Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

Adult 

M 

5  900000 

40,000 

Diff  1  000  cells*  Adult  cells  93  per  cent  • 

2 

M 

6,400,000 

33,000 

young  cells,  7;  eosinophiles,  0. 
(Otitis  *)  question  of  typhoid 

3 

23 

M. 

6,000,000 

27,500 
16,500 

95 

March  16th;  cerebro-spinal. 
"      18th 

4 
5 

15  mos. 

F. 
M 

5,020,000 

19,500 
16  000 

73 

6 

26 

M 

16,000 

7 

20 

F 

15  784 

'   ' 

8 

2 

M 

14200 

Basilar*  no  tuberculosis  in  family  had 

9 
10 
U 

22 
35 
26 

M. 
M. 
M 

4,356,000 

"5*040  oo'o  " 

14,000 
11,700 
11  200 

72 

pneumonia. 
Specific 

Cerebro-spinal  meningitis  (see  Cases  3  and  7,  Table  XXII.) 
shows  the  same  characteristics  in  the  blood  as  do  cases  limited 
to  tjbe  cerebral  meninges.  A  case  reported  by  v.  Jaksch2  had 
4,800,000  red  and  24,000  white  cells. 

1  "Practice  of  Medicine,"  2d  edition. 

2Zeit.  f.  klin.  Med.,  1893,  p.  187. 


EPIDEMIC   CEREBROSPINAL   MENINGITIS. 


249 


EPIDEMIC   CEREBRO-SPINAL  MENINGITIS. 

Williams  finds  leucocytosis  in  about  two-thirds  of  his  cases. 

The  following  cases  were  seen  during  the  epidemic  of  1897. 
The  red  cells  are  not  markedly  affected.  Leucocytosis  is  the 
rule,  but  is  not  invariable.  In  a  general  way  the  higher  the 
count  the  severer  the  case,  and  the  count  usually  rises  as  the 
case  gets  worse  and  falls  with  improvement,  though  often  very 
slowly. 

TABLE  XXIII. —EPIDEMIC  CEREBRO-SPINAL  MENINGITIS. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Percent 
haemo- 
globin. 

Remarks. 

60 

9, 

M. 
M 



51,200 

43,800 

100 

Polynuclear  cells,  95  per  cent. 
April  26th. 

45 

F 

14,600 
16,800 
40,000 

— 

April  28th. 
May  7th,  convalescent. 
Polynuclear  cells,  94  per  cent. 

28 
5 

M. 

M 

35,  600 
26,400 
27,000 
14,000 
13,600 
14,400 
10,300 
35,000 

57 

November  18th. 
November  20th. 
November  22d. 
November  24th. 
November  27th. 
November  29th. 
December  4th,  well. 
March  13th   poly  nuclear  cells,  72  per 

40 

F 

36,300 
24,400 
23,100 
35,  000 

cent. 
March  14th. 
March  18th. 
March  23d,  recovery. 
Polynuclear  cells   93  per  cent 

40 
42 

M. 
M 

5,360,000 

32.000 
30  000 

Polynuclear  cells,  82  per  cent. 

4 

M 

28,800 

69 

September  24th. 

9 

F 

15,800 
12,000 
26  600 

October  1st. 
October  10th,  well. 
July  4th 

mos. 
27 

M 

20,200 
28,000 
17,800 
27,400 
16,000 
11,700 
26  000 

'  48 

Julv  13th. 
July  18th. 
July  22d,  normal. 
July  28th,  temperature  104° 
August  2d. 
August  13th,  temperature  normal. 
July  12th 

18 

M 

31,200 
27  200 

July  17th. 
July  6th 

mos. 

7 

F 

22,300 
*  25  300 

.... 

July  7th. 
March  26th 

21,400 
26,  300 
12,900 

.... 

March  30th. 
April  4th. 
April  13th. 
April  15th,  discharged  well. 

250 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


TABLE  XXIII. — EPIDEMIC  CEREBRO-SPINAL  MENINGITIS  (Continued). 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Percent 
haemo- 
globin. 

Remarks. 

25 

F 

25  000 

Polynuclefir  cells    91  p6r  cent  *  sun- 

22 

M 

24  200 

100 

posed  grippe. 
September    6th 

24 

F 

11,800 
11,300 
23  600 

76 

September  10th. 
September  13th,  recovery. 
October  2d 

33 

M 

10,'  600 
9,600 
7,000 
20  600 

'58 
60 

October  18th 
November  15th. 
November  27th,  recovery. 

31 

M 

19,  500 

55 

Autopsy. 

12 

F 

19  000 

March  13th 

40 

F 

22,400 
26,400 
23,900 
20,  900 
23,400 
14,  600 
19,000 



March  16th. 
March  23d. 
March  31st. 
April  5th. 
April  12th. 
May  24th,  recovered. 

5 

M 

18  800 

March  18th 

31 

M 

16,400 
21,000 
18,000 

62 

March  30th. 
April  3d. 

26 

M 

17,  700 

68 

21 

M 

16  200 

60 

October  3d 

10 

M 

19,  100 
10,000 
11,400 
15  300 

October  4th. 
October  15th. 
Dctober  28th,  became  chronic. 
October  5th 

26 

M 

16,  900 
14,  500 
16,400 
14,400 
17,200 
14  600 

75 

October  7th. 
October  9th. 
October  13th. 
October  15th. 
October  17th  ;  18th  discharged  welL 

20 

F 

14  800 

73    1 

•  0 

Died 

?r9 

F 

13  800 

November  18th 

fl8 

F 

20,700 
14,600 
12  800 

'  80* 

November  21st. 
November  26th,  recovery 

9 

M 

12  400 

80 

October  10th 

32 

F 

17,900 
14,600 
12  400 

October  llth. 
October  12th. 
September  16th 

95 

M 

14,000 
12  100 

'  80' 

September  19th. 
Autopsy  •  serum  reaction  absent., 

18 

M 

11,700 

October  3d 

26 

F 

22,  300 
18,100 
10  700 

95 

October  4th. 
October  5th,  autopsy. 
June  14th 

14,400 

June  24th,  died. 

EPIDEMIC   CEREBRO-SPINAL  MENINGITIS. 


251 


TABLE  XXIII. — EPIDEMIC  CEREBRO-SPINAL  MENINGITIS  (Continued). 


Per  cent 

Age. 

Sex. 

Red  cells. 

White 
cells. 

haemo- 

Remarks. 

globin. 

24 

M. 

10,  000 

June  6th. 

7,600 

June  8th. 

15,600 

' 

June  9th. 

16,200 

June  10th,  temperature  rising  with. 

count. 

12,  300 

June  llth. 

16,700 

June  13th. 

18,800 

June  15th. 

17,800 

June  17th. 

17,800 

June  18th. 

12,100 

June  19th,  temperature  down. 

13,300 

^ 

June  21st. 

16,300 

June  22d,  temperature  up. 

16,400 

June  23d. 

10,  700 

June  25th,  temperature  normal. 

11,700 

July  1st. 

22 

M. 

6  500 

60 

Autopsy. 

L  \AV\S  JJUJ 

Flexner  and  Barker,  investigating  a  large  epidemic  at 
Lonaconing,  Maryland,  found  leucocytosis  in  every  case  (12,000 
-32,000  per  cubic  millimetre).  The  epidemic  studied  by  Wil- 
liams and  myself  was  apparently  due  to  the  diplococcus  in- 
tracellularis  of  Weichselbaum. 

Diagnostic   Value. 

Meningitis  is  the  only  intracranial  disease  (except  abscess 
and  apoplexy)  which  shows  leucocytosis,  and  this  fact  may  be 
of  great  help  in  excluding  other  causes  of  coma. 

1.  Brain    tumor,    hysteria,    lead    encephalopathy,   diabetic 
coma,  sunstroke, '  and  narcotic  or  alcoholic  intoxication  do  not 
cause  leucocytosis  and  hence  can  be  excluded  by  its  presence. 

2.  Uraemia,   apoplexy,  and   post-epileptic  coma   may  have 
leucocytosis  and  cannot  be  distinguished  from  meningitis  when 
leucocytosis  is  present;  but  the  absence  of  leucocytosis  excludes 
meningitis. 

3.  Some  cases  of  typhoid,  when  seen  for  the  first  time  and 


1  In  a  case  of  heat  exhaustion  (temperature  104°)  without  coma,  a  leu- 
cocyte count  of  27, 200  is  recorded  at  the  Massachusetts  Hospital. 


SPECIAL   PATHOLOGY    OF   THE    BLOOD. 

without  a  history  of  the  previous  i'llness,  may  be  difficult  to  dis- 
tinguish from  meningitis,  but  typhoid  never  has  leucocytosis  if 
uncomplicated  and  meningitis  always  has. 

4.  From  pneumonia  we  cannot  distinguish  meningitis  by  the 
blood  count. 


PART  III. 

CHRONIC  INFECTIOUS  DISEASES. 


CHAPTER    VI. 

TUBERCULOSIS. 

RED  COKPUSCLES  AND  HAEMOGLOBIN. 
(a)  Quantitative  Changes. 

I.  THE  striking  fact  is  the  absence  of  such  anaemia  as  we 
should  expect,  judging  from  the  pallor  of  the  patients  and  the 
nature  of  the  disease.     It  is  common  to  find  a  normal  or  even  in- 
creased number  of  red  cells  in  pale  cachectic-looking  consump- 
tives.    We  cannot  help  wondering  whether  our  methods  of  ex- 
amination are  at  fault,  that  is,  whether  the  drop  we  examine  is 
typical.     (For  discussion  of  the  subject  see  page  81.)     However 
this  may  be,  it  is  undoubtedly  the  fact  that  in  most  cases  of 
tuberculosis,  even  in  advanced  stages,  the  count  of  red  cells  is 
approximately  normal.     Often  the  haemoglobin  is  also  high. 

II.  In  a  smaller  number  of  cases  the  haemoglobin  is  much 
diminished,   although    the    count  of    red  cells    is  normal — in 
other  words,  we  find  the  blood  characteristic  of  a  moderately 
severe  secondary  anaemia.     The  red  cells  are  numerous  enough, 
but  only  because  their  numbers  have  been  recruited  by  the  influx 
of  "  half-baked"  or  decrepit  corpuscles,  small-sized  and  pale, 
poor  in  albumin  and  haemoglobin. 

The  condition  differs  from  that  of  chlorosis  mainly  in  that 
some  of  the  red  cells  are  normally  developed  and  nourished, 
while  in  chlorosis  all,  or  nearly  all,  are  feeble.  Such  blood  oc- 
curs in  the  severer  and  more  cachectic  sufferers  from  tubercu- 
losis, just  often  enough  to  make  us  wonder  that  it  is  not  always 
to  be  found. 

III.  In   a  small  percentage  of    cases  both    red    cells    and 
haemoglobin  are  considerably  diminished  (vide  Table  XXIII., 


"254  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

case  32),  the  latter  usually  suffering  more  than  do  the  actual 
number  of  cells,  that  is,  the  color  index  is  usually  below  1. 

Yon  Limbeck1  has  recorded  a  case  in  which  in  the  course  of 
a  tubercular  process  (acute  rniliary)  the  red  cells  fell  as  low  as 
730,000  (white  cells,  4,300;  haemoglobin,  twenty-five  percent). 
But  the  account  of  the  blood  is  not  sufficiently  explicit  in  this 
case  to  enable  us  to  exclude  a  true  pernicious  anaemia  in  the 
course  of  which  the  tuberculosis  may  have  been  only  the  last  in- 
cident. No  other  such  case  is  on  record,  so  far  as  I  am  aware. 

IV.  Fibrin  is  not  increased  unless  extensive  secondary  in- 
fection is  present. 

(6)  Qualitative  Changes. 

I.  There  may  be  none  whatever. 

II.  There  may  be  only  a  pallor  of  some  of  the  individual 
corpuscles  with  slight  changes  in  size  and  shape. 

III.  In  very  severe  cases  the  poikilocytosis  may  be  extreme, 
but  this  is  much  rarer  than  in  many  other  cachexias  of  the  same 
severity  (e.g.,  malignant  disease). 

IV.  An  important  point  is  the  usual  absence  of  nucleated  red 
cells.     Even  after  hemorrhages  it  is  rare  to  find  any  nucleated 
red  cells,  and  this  is  in  marked  contrast  with  cancer  cases,  in 
which  nucleated  red  cells  are  the  rule. 

V.  The  degenerative  changes  described  by  Maragliano  are 
sometimes  found  in  severe  cases  with  mixed  infection  (vide  infra). 

As  regards  the  influence  of  the  different  seats  of  tubercular 
disease  (meningeal,  pulmonary,  genito-urinary,  acute  miliary, 
etc.)  upon  the  red  corpuscles  and  haemoglobin  the  following  are 
the  probabilities. 

Pure  tubercular  disease  itself,  whatever  its  seat,  has  little 
•or  no  effect  upon  the  blood.  The  widely  different  conditions  of 
the  blood  found  in  different  cases  depend  probably  on  the  pres- 
ence or  absence  of  various  other  organisms  (diplococcus  lanceo- 
latus,  pyogenic  cocci)  associated  with  the  tubercle  bacillus,  and 
on  whether  there  is  some  drain  on  the  body  albuminoids  (diar- 
rhoea, peritoneal  effusion,  starvation,  prolonged  suppuration). 
When  the  infection  is  a  mixed  one,  the  blood  shows  the  ordi- 
nary effects  of  septicaemia  (for  then  the  case  is  practically  one 
of  septicaemia)  in  lessening  the  number  and  quality  of  the  red 

i  Loc.  tit.,  p.  380. 


PHTHISIS.  255 

cells.  When  there  is  drain  on  the  fluids  and  proteid  constit- 
uents of  the  body,  the  red  cells  may  not  seem  to  be  diminished, 
owing  to  the  concentration  of  the  blood  from  loss  of  fluid.  Under 
such  circumstances  they  may  even  seem  increased,  but  the  indi- 
vidual corpuscles  are  sure  to  be  lacking  in  haemoglobin  and  the 
other  nitrogenous  bodies  of  which  they  largely  consist. 

Fever  may  be  present  without  there  being  any  changes  in 
the  red  cells  that  we  can  detect.  It  is  only  septic  fever,  and  not 
the  fever  of  pure  tuberculosis  that  drains  the  corpuscles  of  their 
vitality  and  lowers  their  numbers. 

LEUCOCYTES. 
(a)  Quantitative  Changes. 

Here,  as  with  the  red  cells,  the  striking  fact  is  the  absence  of 
changes  in  pure  tuberculosis.  It  makes  no  difference  whether 
we  are  dealing  with  tuberculosis  of  the  bones,  serous  membranes, 
or  internal  organs.  So  long  as  the  infection  remains  unmixed 
the  white  cells  are  not  increased.  In  certain  localities  (lungs, 
kidneys)  the  opportunities  for  a  secondary  infection  and  septi- 
caemia are  so  great  that  we  frequently  find  evidence  of  it  in  the 
blood.  On  the  other  hand,  psoas  abscesses  before  they  are 
opened  often  contain  only  tubercle  bacilli,  and  the  blood  of  such 
cases  shows  no  considerable  changes. 

So  much  more  is  known  of  the  numerical  variations  of  the 
leucocytes  in  tuberculosis  than  of  the  other  blood  constituents, 
that  I  shall  give  a  separate  account  of  them  in  phthisis,  in  tu- 
bercular bone  disease,  in  tubercular  meningitis,  acute  miliary 
tuberculosis,  genito-urinary  tuberculosis,  and  tubercular  peri- 
tonitis. 

I.  PHTHISIS. 

I.  In  incipient  phthisis  the  leucocytes  are  normal  except  after 
haemoptysis. 

II.  After  attacks  of  hcemoptysis,  there  is  usually  leucocytosis, 
subject  to  wide  variations  according  to  the  amount  of  the  hemor- 
rhage and  the  resisting  power  of  the  patient. 

This  follows  the  laws  of  ordinary  post-hemorrhagic  leucocy- 
tosis (vide  supra)  and  disappears  quickly  when  the  hemorrhage 
ceases. 

III.  Cavities. — Very  constantly    accompanied    by    leucocy- 


256  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

tosis.     Indeed  the  absence  of  leucocytosis  in  any  case  proves 
the  absence  of  any  cavity  of  considerable  size. 

IV.  Extensive    infiltration    ("tubercular    pneumonia")    may 
cause  marked  increase  of  white  cells,  sometimes  as  great  as  in 
croupous  pneumonia,  but  this  is  not  invariable. 

V.  Fibroid  Phthisis  (chronic  interstitial  pneumonia). — As  a 
rule  the  leucocytes  show  no  increase,  but  if,  as  sometimes  oc- 
curSj  we  have  the  combination  of  this  condition  with  cavity  for- 
mation, the  latter  may  increase  the  count  of  white  cells. 

VI.  fever. — When  the  temperature  is  normal  the  leucocytes 
are  normal,  but  a  febrile  state  may  or  may  not  be  accompanied 
by  leucocytosis  (according,  presumably,  as  the  fever  is  or  is  not 
due  to  pyogenic  organisms). 

VII.  Tuberculin  Injections. — At  the  height  of  the  reaction 
fever  the  leucocytes  almost  always  rise,  the  lymphocytes  and 
eosinophiles  being  relatively  increased. 

In  a  general  way,  the  worse  the  case  the  higher  the  leucocyte 
count,  yet  the  signs  may  be  advanced  without  causing  any  leu- 
cocytosis if  cavities  are  absent. 

The  following  tables  give  some  idea  of  the  range  of  the  counts 
in  average  hospital  cases  of  phthisis. 


PHTHISIS— RED  CELLS. 

Between  2, 000, 000  and  3, 000, 000  =    1  case. 
3,000,000    "     4,000,000  =  18  cases. 
4,000,000    "     5,000,000  =  25      " 
5,000,000    "     6,000,000  =  16      " 

Total 60      " 

PHTHISIS — HEMOGLOBIN. 

From  10  to    20  per  cent  =    1  case. 

"  20  "  30  =0     " 

"  30  "  40  "  =    4  cases. 

"  40  "  50  "  =    6      " 

"  50  "  60  "  =  19      " 

"  60  •'  70  "  =  23      " 

"  70  "  80  "  =  16      " 

"  80  "  90  "  =6      " 

"  90  "   100  "  =    5      " 

Total..  ..80      « 


PHTHISIS.  257 


PHTHISIS— WHITE  CELLS. 
Between    3, 000  and    4, 000  —      5  cases. 


4,000 

"   5,  000  = 

4 

5,000 

"   6,000  = 

9 

6,000 

"   7,  000  = 

9 

7,000 

"   8,  000  = 

10 

8,000 

"   9,000  = 

9 

9,000 

"  10,  000  = 

14 

10,  000 

"  11,000  = 

5 

11,000 

"  12,000  = 

7 

12.  00£ 

u  15,000  = 

25 

15,000 

"  20,000  = 

16 

20,000 

"  30,  000  = 

8 

30,000 

"  40,000  = 

3 

Total 124      " 

The  number  of  those  showing  leucocytosis  is  slightly  greater 
than  those  without  it,  probably  because  incipient  cases  rarely 
think  themselves  sick  enough  to  come  to  a  hospital.  On  the 
other  hand,  some  of  the  cases  which  appear  to  have  been  going 
on  for  months  have  normal  leucocyte  counts.  The  duration  is 
less  important  than  the  nature  and  severity  of  the  process.  It 
is  rare  to  see  extensive  signs  in  the  lungs  without  leucocytosis — 
fibroid  phthisis  excepted. 

Qualitative  Changes  in  the   White  Cells. 

1.  Many  cases  show  none  at  all. 

2.  When  the  leucocyte  count  is  normal  we  may  find  an  in- 
creased percentage  of  large  and  small  lymphocytes,  such  as  is 
commonly  found  in  any  blood  poor  in  nutritive  qualities  (see 
page  96). 

3.  "When  leucocytosis  is  present,  we  usually  find  the  ordi- 
nary marked  increase  in  the  percentage  of  polymorphonuclear 
cells  at  the  expense  of  the  lymphocytes. 

For  example :  C.  D ,  male,  thirty-two  years  old.  Tuber- 
culosis of  lungs,  with  cavities;  leucocytes,  17,580.  Differentia] 
count  of  1,000  cells  shows : 

Per  cent. 

Polymorphonuclear 83.4 

Lymphocytes  (small) 8.2 

Laa-ge  lymphocytes  (large  and  transitional) 8.4 

Eosinophiles .". .  r 0. 

17 


258  SPECIAL    PATHOLOGY    OF   THE    BLOOD. 

4.  Eosinopliiles  are  increased  during  the  reaction  from  an 
injection  of  tuberculin,  and  also  in  some  cases  with  cavities  in 
which  possibly  the  individual  inoculates  himself  with  tuberculin 
manufactured  in  the  cavities  of  his  own  lungs. 

Otherwise  the  eosinophiles  are  increased  only  at  certain 
physiological  seasons — menses  and  coitus.  In  most  cases  asso- 
ciated with  leucocytosis  they  are  absent. 

5.  Myelocytes  were  found  by  Holmes,  W.  R.  May,  and  my- 
self in  many  cases  of  advanced  phthisis.     They  averaged  .3  per 
cent. 

Perinuclear  BasopJiilia.  * 

\ 

Neusser  and  his  followers  have  advanced  a  theory  that  the 
occurrence  of  perinuclear  basophilia  during  tuberculosis  is  a 
favorable  sign  and  marks  a  system  capable  of  resisting  the 
tubercular  infection.  The  researches  of  Futcher  and  my  own 
attempts  to  verify  Neusser 's  theory  have  not  confirmed  his 
findings. 

Holmes,  of  Denver,  has  studied  the  leucocytes  in  phthisis 
with  great  care  and  considers  that  he  finds  therein  means  not 
only  of  diagnosing  tuberculosis  by  the  blood  alone,  but  of 
measuring  the  degree  of  advancement  of  the  process  and  the 
amount  of  resisting  power  in  the  patient. 

I  have  carefully  followed  out  Holmes'  procedures  with  stains 
seen  and  approved  by  him.  I  can  verify  most  of  his  statements 
of  fact,  but  some  of  the  inferences  which  he  draws  therefrom 
are,  I  think,  wholly  unwarranted.  The  blood  changes  in  pul- 
monary tuberculosis  are  mainly  such  as  he  describes,  but  they 
have  no  diagnostic  value,  as  similar  changes  are  found  in  a 
great  variety  of  other  diseased  conditions.  The  increase  of 
polymorphonuclear  forms  in  advanced  cases,  the  increased 
amount  of  "debris,"  the  degenerating  forms,  etc.,  are  all  char- 
acteristic not  of  tuberculosis  alone  but  of  any  severe  suppurative 
process.  The  increase  of  "  debris"  is  probably  the  same  datum 
which  Watkins  interpreted  as  an  increase  in  blood  plates 
and  Goldberger  and  Weiss  as  "  extracellular  glycogen. "  (With 
Holmes'  "  undeveloped  nuclei"  in  the  leucocytes,  compare  page 

121  ) 

1  See  Appendix. 


BONE  TUBERCULOSIS.  259 

II.  BONE  TUBERCULOSIS. 

Brown '  has  studied  seventy -two  cases,  Dane 2  forty-one. 
Dane's  study  of  the  blood  in  forty-one  cases  of  hip  disease  and 
Pott's  disease  is  a  very  careful  one.  Whenever  abscesses  ap- 
peared in  connection  with  the  disease,  cultures  were  taken  when 
the  abscess  was  first  opened  and  again  later  on,  and  the  coin- 
cidence of  low  counts  with  absence  of  pyogenic  cocci  and  with 
high  counts  of  secondary  pyogenic  infection  is  very  notable. 
Dane's  conclusions  are  as  follows : 

1.  "High  leucocyte  counts,  especially  in  hip  disease,  point 
to  the  probability  that  there  is,  or  soon  will  be,  abscess  forma- 
tion; but  low  counts  do  not  preclude  the  presence  of  abscess, 
especially  in  long-standing  cases. 

2.  "If  abscess  is  present,  a  low  count  of  white  cells  indicates 
the  absence  of  secondary  pyogenic  infection  (proved  by   cul- 
tures) . 

3.  "  Cases  of  traumatic  origin  are  generally  accompanied  by 
a  high  leucocyte  count. 

4.  "  The  leucocyte  count  bears  no  direct  relation  to  the  tem- 
perature;   one  case  with  30,980  leucocytes  (five-year-old  girl) 
showed  a  temperature  of  only  99.4°  at  the  time  of  the  count.     In 
another  girl  of  three  years  whose  temperature  ranged  between 
101°  and  104°,  the  leucocytes  were  only  7,224,  or  subnormal  for 
that  age  (vide  infra,  page  336). 

5.  "Cases  where  at  the  primary  operation  the  pus  proved 
sterile  show  an  increase  in  the  leucocyte  count  when  the  wound 
becomes    infected  with    pyogenic    organisms"    (as    it    always 
does) . 

6.  "  The  red  cells  are  rarely  diminished,  but  the  haemoglobin 
is  usually  relatively  low  (mild  secondary  anaemia  in  these  cases) . 
This  absence  of  a  diminution  in  the  red  cells  in  these  cases  is 
the  more  remarkable  because  they  were  almost  all  in  young  chil- 
dren whose  blood  is  much  more  sensitive  to  any  deleterious  in- 
fluence than  that  of  adults." 

Brown  dissents  from  several  of  Dane's -conclusions.  He 
thinks  that  a  case  may  go  on  to  abscess  formation  without  any 
increase  in  the  leucocyte  count.  When  an  increase  does  take 

1  Transactions  of  California  Medical  Society,  1897. 

2  Boston  Medical  and  Surgical  Journal,  May  28th,  1896. 


260  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

place  he  thinks  it  due  either  to  a  secondary  infection  or  to  an 
increased  activity  of  the  tubercular  process  itself  without  any 
secondary  infection.  The  latter  process,  however,  in  Brown's 
experience  causes  only  a  moderate  increase  (2,000-3,000), 
while  if  a  marked  increase  suddenly  or  gradually  occurs  he 
thinks  it  "most  significant  of  secondary  infection."  With 
Dane's  fifth  conclusion  he  wholly  agrees  and  adds:  "After  the 
infection  (produced  by  the  operation)  the  leucocytosis  is  very 
high  for  a  time,  and  if  the  sepsis  is  acute  and  threatens  life  it 
remains  high  until  the  crisis  is  passed."  Otherwise  it  grad- 
ually falls  after  the  first  few  days,  and  if  the  patient  progresses 
well,  it  disappears.  If  the  pyogenic  matter  overcomes  the  re- 
cuperative power,  the  leucocytes  fall  as  in  peracute  pneumonia 
or  peritonitis.  In  such  cases  the  anaemia  increases  as  well. 

Qualitative  Changes. 

(a)  As  in  other  forms  of  tuberculosis  there  may  be  none  at 
all.  (b)  The  cell  changes  in  purely  tubercular  cases  is  illustrated 
well  by  Case  17  of  Dane's  series,  a  boy  of  seven  whose  blood  on 
the  day  of  operation  for  hip  disease  with  large  abscess  showed 
8,932  leucocytes.  The  differential  count  was  as  follows: 

Per  cent. 

Polymorphonuclear  neutrophiles 40 

Small  lymphocytes 49 

Large  lymphocytes  and  transitional  forms 8 

Eosinophiles  ... 3 

Eight  ounces  of  pus  were  evacuated,  in  which  cultures  showed 
the  absence  of  pyogenic  organisms. 

This  case  demonstrates  that  some  cases  of  tubercular  sup- 
puration have  no  tendency  to  produce  leucocytosis  or  to  increase 
in  the  neutrophiles,  but  influence  the  blood  only  by  producing 
what  might  be  termed  a  functional  debility  of  the  blood  through 
lack  of  nutritive  substances  in  the  plasma.  This  condition 
is  by  no  means  peculiar  to  tuberculosis,  but  occurs  in  a 
great  variety  of  debilitated  or  cachectic  conditions,  as  already 
stated. 

(c)  But  when  a  septicaemia  complicates  the  tuberculosis,  cell 
metamorphosis  appears  to  be  accelerated,  and  we  get  with  the 


ACUTE   MILIARY   TUBERCULOSIS. 


261 


quantitative  increase  of  leucocytes  such  qualitative  changes  as 
the  following : 

Per  cent. 

Polyraorphonuclear  neutrophiles 84 

Lymphocytes  (small) 9 

Lymphocytes  (large  and  transitional) 6 

Eosinophiles 1 

This  was  a  case  (No.  33  of  Dane's  series)  in  which  the  ab- 
scess, sterile  when  first  opened,  had  become  inoculated  with  the 
staphylococcus  aureus. 

(d)  Not  every  case  with  leucocytosis  shows  qualitative 
changes  as  the  above.  One  of  Dane's  cases  (No.  22,  a  boy  of 
saven)  showed  a  leucocytosis  of  23,387,  but  only  sixty  per  cent 
of  these  were  polymorphonuclear,  and  two  per  cent  eosinophiles. 

In  a  case  recorded  by  Dane  (No.  32),  tubercular  osteomyelitis 
showed  6,083  white  cells  (subnormal,  as  the  child  was  only  two 
years  old)  with  sixty -four  per  cent  of  polymorphonuclear  cells. 
The  pus  from  the  bone  cavity  showed  no  pyogenic  organisms 
on  culture.  Ordinary  septic  osteomyelitis  gives  very  different 
results  (see  page  234) .  Dane's  cases  were  almost  exclusively 
hip  and  spinal  affections. 

The  following  cases  from  the  Massachusetts  Hospital  records 
illustrate  tuberculosis  of  .other  bones : 


Case. 

Diagnosis. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

1 

Tuberculosis  of  the  knee  joint  

6,472,000 

9  400 

63 

2 

t(       •             u                         it 

2,704,000 

8,000 

? 

3 

Metatarsal  tuberculosis 

4  650  000 

6  500 

61 

4 

Tubercular  rib  ...           .... 

5  016  000 

5  800 

73 

III.  ACUTE  MILIARY  TUBERCULOSIS. 

i 

Probably  there  are  no  important  changes  in  the  red  cells  or 
haemoglobin.  The  number  of  cases  on  record  is  too  small  to 
enable  me  to  speak  positively  on  this  point,  but  the  acuteness  of 
the  disease  would  lead  us  to  expect  the  normal  or  approximately 
normal  conditions  recorded  in  the  few  published  cases. 
About  the  leucocytes  we  know  more. 


262 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


Quantitative  Changes. 

Normal  or  subnormal  counts  are  the  rule.  When  occasion- 
ally there  occurs  a  leucocytosis  it  may  be  inferred  that  the 
miliary  process  accompanies  a  suppurative  one,  and  that  the 
latter  and  not  the  former  is  responsible  for  the  increased  number. 

Warthin1  reports  a  case  with  autopsy  in  which  he  made  over 
thirty  counts  of  the  white  corpuscles,  verifying  the  more  re- 
markable results  by  repetition.  Autopsy  showed,  besides  mil- 
iary tuberculosis,  a  cavity  in  the  lower  lobe  of  the  right  lung 
and  a  suppurating  focus  about  the  seminal  vesicles  containing 
four  ounces  of  pus  rich  in  tubercle  bacilli.  Whether  pyogenic 
organisms  were  also  present  is  not  stated.  The  leucocyte 
counts  were  as  follows : 


Day. 

Hour. 

Leuco- 
cytes. 

Remarks. 

December  6th 

10  A.M. 

3,500 

12th 

8  A.M. 

5,000 

18th 

5  P.M. 

3,500 

22d 

10  A.M. 

5,625 

22d 

11:  30  A.M. 

4,725 

22d 

3  P.M. 

5,000 

22d 

5P.M. 

3,125 

24th 

8:  30A.M. 

3,750 

24th 

11:30  A.M. 

3,750 

24th 

2  P.M. 

2,500 

24th 

4:  30  P.M. 

2,500 

25th 

28th 

8  A.M. 

5:  30  P.M. 

1,875 
3,750 

[80  per  cent 
Red  cells,    4,125,000;     haemoglobin, 

29th 

10  A.M. 

1,250 

29th 

2  P.M. 

1,250 

29th 

5:  30  P.M. 

3,750 

31st 

12  M. 

1,250 

31st 

6P.M. 

2,500 

Jan  ary  2d 

11  A.M. 

1,250 

2d 

5P.M. 

2,500 

3d 

2:  30  P.M. 

600 

Severe  chill.    Count  repeated  several 

times. 

5th 

8:  30A.M. 

3,750 

5th 

11  A.M. 

3,137 

5th 

4P.M. 

8,125 

Moribund. 

6th 

9  A.M. 

10,000 

6th 

10  A.M. 

5,625 

6th 

11  A.M. 

2,500 

"       '  6th 

12  M. 

5,625 

6th 

12:  50  P.M. 

Death. 

Medical  News,  1895. 


•ACUTE   MILIARY   TUBERCULOSIS. 


263 


In  another  case  lie  found  also  a  subnormal  count.  Bieder 
found  normal  counts  in  two  cases.  Von  Limbeck  states  that 
the  leucocytes  are  normal,  but  gives  no  counts. 

The  following  cases  from  the  Massachusetts  Hospital  records 
illustrate  these  points : 

ACUTE  MILIARY  TUBERCULOSIS. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

28 
5°! 

M. 
F 

2,448,000 

550 
1,200 
1,100 

1,300 
3  500 

35 
90 

March    8th. 
March  llth. 
March  llth,  gave  protonuclein  gr. 
xv.  t.  i.d. 
March  13th,  differential  count  (see 
below). 
March  14th,  glands  rapidly  dimin- 
ishing. 
March  18th,  died.     Autopsy. 

18 

M 

3,600 

Autopsy. 

40 
14 
51 
?-3 

M. 
F. 
M. 
M 

3,  780,  bob 

4,664,000 

3,750 
4,400 
4,800 
4,900 

45 

Autopsy. 
Autopsy. 
Autopsy.     Chronic  phthisis  also. 
Autopsy.    Differential  count  normal 

18 

F 

5.400 

80 

September  21st. 

29 
12 

M. 

F 

7,400 
5,600 
6  100 

'ii- 

September  24th,  no  serum  reaction. 
Autopsy.     No  serum  reaction. 
Autopsy. 

19 
37 
20 

F. 
F. 

F 



6,600 

7,  500 
7,800 

*n 

Autopsy. 
Autopsy. 
May  14th. 

36 
30 

M. 
M 

7,200 
7,600 
9,250 

May  22d.     Autopsy. 
Healed  phthisis  also.     Autopsy. 
April  18th. 

45 
22 

M. 
M. 

5,237,000 

9,450 
10,  000 
12,700 

.... 

April  20th.     Autopsy. 
Autopsy. 
Phthisis  also.     Autopsy. 

Case  I.  of  the  above  table  is  a  striking  example  of  the  re- 
markably low  leucocyte  count  sometimes  seen  in  this  disease. 
The  counts  were  carefully  verified  by  several  competent  ob- 
servers. The  differential  count  made  on  the  13th  showed : 

Polymorphonuclear  neutrophiles 78  per  cent. 

Lymphocytes  (small) 12        " 

Lymphocytes  (large) 9        " 

Eosinophiles , 1        " 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


Qualitative  Changes. 

In  Warthin's  case  above  quoted,  he  repeatedly  made  differ- 
ential counts  of  the  leucocytes  by  Ehrlich's  methods  with  this 
average  result: 

Per  cent. 

Polymorphonuclear  neutrophiles 91.49 

Lymphocytes  (small) 5.52 

Lymphocytes  (large  and  transitional) 3.09 

Eosinophiles 0. 

Myelocytes 2 


IV.  TUBERCULOSIS  OF  SEROUS  MEMBRANE. 
1.  TUBERCULAR  PERITONITIS. 

The  blood  condition  is  exactly  as  in  other  forms  of  tubercu- 
losis, except  in  so  far  as  it  is  modified  by  the  drain  exerted  on 
the  blood  by  diarrhosa  or  by  transudation  or  exudation  into  the 
peritoneal  cavity.  Such  events  concentrate  the  blood  by  with- 
drawing water  and  albumin  from  it  and  may  give  us  a  normal 
number  of  red  cells  per  cubic  millimetre,  when  in  reality  a  con- 
siderable anaemia  is  present.  As  a  rule,  the  blood  shows  a  mild 
secondary  anaemia  without  leucocytosis  or  with  leucopenia. 
This  is  exemplified  in  the  following  tables  from  the  Massa- 
chusetts Hospital  records : 


Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

26 
33 
24 

F. 
F. 
M 

3,120,000 
2,900,000 
5,  360,  000 

2,240 
3,800 
3,800 

58 
48 

January  6th,  1896 

25 

F. 

5,760,000 

5,600 
3,900 

85 

April  13th,  1896. 
Tubercular  tube. 

21 

M. 

4,400 

27 

M 

4  900 

64 

March  1st 

43 

M 

5,500 
5  000 

March  9th. 
December  18th,  1895 

30 

F. 

4,560,000 

3,250 
5,183 

76 

January  10th,  1896. 
Tubercular  tube. 

20 
44 

F. 
M. 

5,936,000 
2,974,000 

5,400 
5,530 

Pleuritic  effusion  also. 

16 
33 
50 
37 

F. 
F. 
F. 
M. 

3,840,000 
4,000,000 
5,240,000 

6,000 
6,000 
6,400 
6,700 

56 

Mav  22d.  1896. 

TUBERCULAR    MENINGITIS. 


265 


Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

30 
44 

M. 
F 

5,  560,  000 

7,000 
6,800 
7,000 

73 

May  30th,  1896. 

26 

17 
32 

M. 
M. 
F. 

4,368,000 
4,904,000 

7,400 
8,000 
8,200 

45 

75 

20 
29 
50 
41 
38 
21 
27 

F. 
F. 
F. 
M. 
F. 
F. 
F. 

4,  200,  000 
3,  400,  000 
4,600,000 
5,200,000 
4,816,000 
3,555,000 

8,500 
8,600 
10,000 
10,000 
11,200 
11,500 
16,900 
18,  300 

58 
30 
50 

65 
76 

Tubercular  tube. 
Pelvic  abscess  also. 

I  know  of  no  differential  counts  of  leucocytes  in  tubercular 
peritonitis.  Presumably  the  sluggish  metabolism  of  the  cells 
found  in  other  forms  of  pure  tuberculosis  exists  here  and  causes 
an  excess  of  the  mononuclear  elements. 

2.  TUBERCULAR  MENINGITIS. 

Kemarkably  few  counts  are  on  record  so  far  as  I  can  ascer- 
tain. Von  Limbeck  gives  but  a  single  case  (with  autopsy). 
Four  counts,  the  last  on  the  day  of  death,  showed  the  follow- 
ing: 

May  22d,     1889  :  Leucocytes 8,000 

"     23d,    1889:          "  8,000 

"     24th,  1889 :          "  6,000 

"     26th,  1889:          "  7,500 

Rieder  records  two  cases,  in  one  of  which  the  leucocytes  were 
"normal  or  subnormal;  in  the  other  increased."  In  both  diag- 
nosis was  confirmed  by  autopsy.  The  counts  in  these  cases 
were  as  follows : 

Case   I.— February  26th,  1891  :  Leucocytes 7,800 

March  2d,  1891  :  Leucocytes 5, 900 

Case  II.— May  30th,  1891  :  Leucocytes 14,400 

Pick1  saw  two  cases : 

Case   I.— February  28th,  1890  :  Leucocytes 6,500 

March  5th,  1890  :  Leucocytes 8, 000 


In  the  second  case  there  was  also  no  leucocytosis.     Autopsy  in 


266 


SPECIAL    PATHOLOGY    OF   THE    BLOOD. 


both.    Sorensen's  '  two  cases  showed  respectively  8,300  and  9,400 
leucocytes.     My  own  results  in  seven  cases  are  as  follows : 


TUBERCULAR  MENINGITIS. 


Aee. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

'21 

M. 

28  000 

63 

July  8th 

34,  300 

July  9th.     Autopsy 

2 

F. 

25,  900 

May  30th 

23,800 

June  4th.    Tubercular  perito- 

32,800 

nitis  also. 
June    8th. 

27,  800 

June  10th 

23,  600 

June  12th 

16,  500 

June  14th. 

21,000 
19,800 

June  16th. 
June  18th. 

34 

M. 

21,500 

Autopsy. 

35 

M 

14  700 

68 

Pleurisy  also 

22 

M. 

14  400 

January  25th 

19,400 

January  30th 

13,200 

February  2d 

19,300 

February  6th      Autopsy. 

45 

M. 

8,000 

Autopsjr. 

24 

F. 

4,590,000 

6,600 

46 

Autopsy. 

These  are,  so  far  as  I  can  ascertain,  the  only  cases  of  uncom- 
plicated tubercular  meningitis  with  autopsy  in  which  blood  ex- 
aminations are  recorded  and  in  all  but  one  of  these  nothing  is 
said  about  red  cells  or  haemoglobin.  Rotch  mentions  a  single 
case  complicated  by  an  appendicitis  in  which  the  following  count 
is  recorded  (girl  of  eleven  years) : 

Red  cells 5,298,750 

White  cells , 37, 500 

Haemoglobin  (per  cent). 68 

Whether  the  leucocytosis  was  due  wholly  to  the  appendicitis 
or  not  we  cannot  tell. 

I  have  examined  no  other  cases  of  uncomplicated  tubercular 
meningitis  in  which  autopsy  confirmed  the  diagnosis.  In  two 
cases  in  which  clinically  the  diagnosis  was  tubercular  meningitis 
I  found  moderate  leucocytosis,  in  one  with  ninety-one  per  cent 
polymorphonuclear  cells.  Two  of  the  cases  of  iniliary  tubercu- 
losis above  mentioned  had  marked  meningeal  symptoms  and 

1  Cited  by  Rieder. 


GLANDULAR   TUBERCULOSIS.  267 

plenty  of  tubercles  in  the  meninges,  but  being  a  general  and  not 
a  local  process  no  conclusions  as  to  the  blood  of  tubercular 
meningitis  can  be  drawn  from  the  absence  of  leucocytosis  in 
these  cases. 

On  the  whole,  it  seems  that  pure  tubercular  meningitis 
differs  markedly  from  other  pure  tubercular  processes,  in  that 
it  has  in  most  cases  a  strong  tendency  to  raise  the  leucocyte 
count..  Osier's  resiilts  point  to  the  same  conclusion.1  Ziemke2 
has  recently  reported  a  case  with  17,500  leucocytes  per  cubic 
millimetre.  The  red  cells  and  haemoglobin  show  probably  the 
same  changes  as  in  other  forms  of  tuberculosis. 

3.  TUBERCULAR  PERICARDITIS. 

In  one  case  in  which  tubercle  bacilli  were  repeatedly  demon- 
strated in  the  fluid  obtained  by  tapping  the  pericardial  sac  I 
found  no  leucocytosis.  I  have  not  met  with  any  other  reports 
on  the  blood  in  this  condition. 

4.  TUBERCULAR  PLEURISY. 

No  doubt  a  large  proportion  of  all  pleuritic  effusions  are 
tubercular  in  origin,  but,  so  far  as  I  have  seen,  no  counts  are  re- 
corded in  cases  proved  by  culture  or  inoculation  to  be  tuber- 
cular. The  low  leucocyte  counts  in  most  pleurisies  (see  above, 
page  211)  tend  to  show  that  they  are  tubercular  and  not  due  to 
pyogenic  organisms. 

Pick  mentions  that  he  finds  no  leucocytosis  in  tuberculous 
pleurisy  when  uncomplicated  by  phthisis,  but  reports  no  actual 
counts. 

5.  GLANDULAR  TUBERCULOSIS. 

In  cases  of  so-called  scrofulous  glands,  whether  in  children 
or  adults,  the  blood  shows  no  important  changes  except  that  in 
children  the  haemoglobin  may  be  considerably  diminished. 

1  Text-book  of  Medicine,  3d  edition. 
JDeut.  med.  Wooh.,  April  8th,  1897. 


26S 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 
GLANDULA.R  TUBERCULOSIS. 


ITo. 

Age. 

Sex. 

White  cells. 

Per  cent 
haemoglobin. 

1  

20 

F. 

5  600 

75 

2  

28 

M 

10  900 

65 

3  

7 

F. 

11  000 

Leucocytosis  is  absent  unless  an  abscess  has  been  opened 
and  infected.  Whether  or  not  tuberculosis  of  the  abdominal  or 
other  internal  lyrnph  glands  affects  the  blood,  I  am  unable  to 
say. 

6.  GENITO-UEINA.RY  TUBERCULOSIS. 

Here  the  opportunities  for  a  secondary  pyogenic  infection 
are  so  good  that  in  well-marked  cases  we  find  the  blood  of 
septicaemia  present.  The  following  cases,  all  involving  the 
bladder,  kidney,  and  the  external  genitals,  illustrate  this  point : 


No. 

Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

1 

2 

3 

30 
41 

22 

M. 
F. 

F 

3,796,000 
3,588,000 
3,000,000  + 

14,452 
10,400 
14,452 
10,200 

44 
55 

4 
5 

35 
22 

F. 
F 

5,808,000 

8,800 
8,400 

65 

70 

6 

31 

M 

7,600 

57 

7 

31 

F. 

6,900 

60 

8 

42 

M. 

7,000 

December  18th. 

8,700 
8,300 

December  26th. 
January  llth. 

SYPHILIS. 

Reiss,  in  an  article  in  the  Arcliiv  f.  Dermatologie  und  Syphilis, 
1895,  Heft  1,  says  that  the  general  constitutional  influence  of  the 
poison  of  syphilis  is  best  indicated  by  the  condition  of  the 
blood.  In  one  hundred  cases  he  has  arrived  at  the  following 
conclusions  regarding  the 

Bed  Cells  and  Hcemoglobin. 

During  the  time  between  the  chancre  and  the  secondary  symp- 
toms, the  red  cells  are  slightly  decreased,  but  this  is  much  more 


SYPHILIS.  269 

marked  after  the  appearance  of  secondary  symptoms  and  con- 
tinues for  a  time  even  after  treatment  has  begun.  The  haemo- 
globin sinks  steadily  from  the  time  of  the  primary  lesion  on, 
but  is  not  especially  affected  by  the  eruption.  Even  under 
treatment  the  haemoglobin  never  gets  quite  up  to  normal  and  pro- 
longed mercurial  treatment  lowers  it,  although  mercury  has  at 
first  a  beneficial  effect  on  the  haemoglobin  as  well  as  on  the  other 
constituents  of  the  blood. 

Konried '  goes  further  into  detail.  According  to  him,  in  the 
first  four  to  seven  weeks  after  infection,  the  number  of  red  cells 
remains  normal,  but  the  haemoglobin  begins  to  fall  off,  losing 
from  ten  to  twenty  per  cent  in  that  time.  Afterwards  it  sinks 
steadily  unitl  treatment  is  begun,  the  number  of  corpuscles  also 
falling  slightly. 

Newmann  and  Kouried,8  reporting  in  1893  on  two  hundred 
cases,  say  that  up  to  the  time  of  the  secondary  symptoms  from 
twenty-five  to  thirty  per  cent  of  haemoglobin  is  generally  lost, 
without  much  change  in  the  red  cells,  which  sink  considerably  in 
number  after  the  outbreak  of  secondary  lesions.  Lezius3  like- 
wise finds  no  diminution  in  the  number  of  red  cells  until  the  out- 
break of  secondary  lesions. 

All  these  changes,  like  those  about  to  be  described,  are  apt 
to  be  more  marked  in  women  than  in  men.  In  cases  going  on 
to  the  secondary  stage  untreated,  the  haemoglobin  may  sink  to 
as  low  as  twenty -five  per  cent.  In  the  tertiary  stages  and  in 
hereditary  and  so-called  "  constitutional  syphilis"  the  red  cor- 
puscles are  much  more  seriously  affected,  diminishing  con- 
siderably in  number  as  well  as  in  weight  and  color.  The 
hereditary  syphilis  of  infancy  may  indeed  produce  fatal 
anaemia  and  very  low  counts  are  common,  with  large  num- 
bers of  nucleated  red  cells  and  great  deformities  in  shape 
and  size. 

The  effect  of  mercurial  treatments  on  the  red  cells  is  interest- 
ing. Gaillard 4  found  that  the  count  of  red  cells  increased  dur- 
ing the  first  fourteen  days  and  the  haemoglobin  during  the  first 
twenty-four  days  of  treatment.  After  that  time,  if  mercury  was 

1  International  Dermatological  Congress,  1892. 
*  Wiener  kliu.  Woch. ,  1893.  No.  19. 
3Inaug.  Dissert.  Dorpat,  1889. 
4  Gaz.  des  Hop.  1885,  No.  74. 


270  SPECIAL    PATHOLOGY    OF    THE   BLOOD. 

still  given,  the  haemoglobin  and  later  the  number  of  corpuscles 
began  to  decline. 

Konried  (loc.  cit. )  found  the  haemoglobin  to  rise  duriug  the 
administration  of  the  first  twenty-five  to  thirty -five  inunctions, 
after  which  it  began  to  go  down.  This  was  in  cases  in  which 
treatment  was  begun  just  after  the  onset  of  secondary  symptoms. 
In  the  worst  cases  it  sank  even  as  low  as  forty -five  per  cent  de- 
spite treatment,  and  this  usually  means  a  bad  prognosis  and 
severe  tertiary  symptoms  to  come.  In  one  of  my  own  cases  the 
haemoglobin  was  only  thirty-seven  per  cent,  though  the  red  cells 
were  4,988,000  (color  index,  .37). 

Potassic  iodide  increases  the  red  cells  and  haemoglobin,  but 
has  no  special  effect  on  the  leucocytes. 

Cases  often  show  spontaneous  improvement  in  their  anaemia 
as  well  as  in  other  symptoms. 

Justus1  in  three  hundred  cases  claims  to  have  observed  a 
peculiar  reaction  of  the  haemoglobin  in  syphilis,  which  does 
not  occur  in  any  other  disease,  and  which  he  considers  of  much 
diagnostic  value. 

According  to  him,  if  in  cases  in  which  secondary  symptoms 
have  not  yet  appeared,  we  test  the  haemoglobin  and  then  give  an 
inunction  or  a  subcutaneous  injection  of  mercury,  we  find  that 
within  twenty -four  hours  a  very  marked  fall  in  haemoglobin  has 
taken  place  (ten  to  twenty  per  cent),  owing  to  the  action  of  the 
mercury  on  the  weakened  corpuscles.  This  sudden  fall  is  fol- 
lowed by  a  gradual  rise  until  within  a  few  days  the  coloring 
matter  is  at  a  point  slightly  higher  than  before  the  mercury  was 
given.  In  diseases  other  than  syphilis  this  sudden  drop  does 
not  occur.  After  the  advent  of  secondary  symptoms  the  pecu- 
liar reaction  to  mercury  does  not  occur. 

No  evidence  for  or  against  this  observation  has  as  yet  been 
brought  forward  by  others.  In  view  of  the  large  number  of 
cases  in  which  Justus  has  tried  the  experiment  it  is  certainly  an 
interesting  observation  and  deserves  to  be  followed  up.  If  true, 
it  might  give  valuable  assistance  in  the  diagnosis  of  doubtful 
cases  before  the  appearance  of  the  "secondaries." 

White  Cells. 

1.  Here  the  changes  are  very  characteristic.  In  the  first 
stage  the  leucocytes  are  either  normal  or  slightly  increased,  but 

1  Verhandl.  d.  5.  Cong.  d.  Deut.  dermatolog.  Gesellschaft,  September, 
1895. 


SYPHILIS.  271 

the  percentage  of  polymorphonuclear  forms  is  almost  always 
notably  low,  and  that  of  the  lymphocytes  high.  If  mercury  is 
given  at  this  stage,  the  polymorphonuclear  forms  begin  to  in- 
crease toward  normal  and  the  lymphocytes  proportionately  to 
decrease.  [Mercury  given  to  healthy  persons  has  just  the  op- 
posite effect,  increasing  the  lymphocytes  at  the  expense  of  the 
polymorphonuclear  forms.]  Iodide  of  potash  works  exactly 
like  mercury  in  this  respect,  increasing  the  polymorphonuclear 
leucocytes  in  syphilis,  while  it  diminishes  them  in  healthy 
persons. 

2.  As  the  eruption  breaks  out  leucocytosis  (12,750  and  16,800 
in  two  of  my  cases)  generally  appears,  the  proportion  of  lym- 
phocytes and  of  eosinophiles  usually  being  increased.  Engel 
describes  a  syphilitic  child  in  whom  the  percentage  of  polymor- 
phonuclear cells  steadily  rose  as  the  child  got  worse.  In  such 
cases  Engel  considers  these  cells  to  be  of  prognostic  importance. 
P.  K.  Brown  has  made  a  similar  observation  in  bone  tuber- 
culosis. Treatment  with  mercury  and  potassium  iodide  tends 
to  bring  down  the  count  of  lymphocytes,  while  it  raises  the 
count  of  red  cells ;  and  among  the  white  cells  to  increase  the 
polymorphonuclear  forms. 

In  the  tertiary  stages,  with  the  severe  anaemia  which  is  often 
present,  there  occur  occasionally  leucocytosis,  not  uncommonly 
with  small  percentages  of  myelocytes,  and  a  marked  lymphocy- 
tosis.  Miiller1  has  described  four  cases  of  anaemia  in  syphilis  so 
severe  as  to  simulate  pernicious  anaemia  very  closely.  In  one 
the  red  cells  sank  to  720,000.  Laache2  mentions  a  similar  case. 

There  are  no  constant  changes  in  the  blood  plates.  Specific 
gravity  follows  pretty  closely  the  haemoglobin  percentage. 

Diagnostic  Value. 

Justus'  reaction  of  syphilitic  blood  to  mercury,  if  true,  might 
be  of  great  value  in  distinguishing  early  syphilis  from  various 
other  causes  of  debility. 

The  occurrence  in  adults  of  leucocytosis  with  increased  per- 
centages of  lymphocytes  and  of  eosinophiles,  is  very  suggestive 
of  syphilis  as  against  tuberculosis,  typhoid  or  malignant  dis- 
ease. In  children,  rickets  and  other  diseases  may  give  similar 

1  Charite-Annalen,  vol.  xiv.  2  LOG.  cit. 


272  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

blood  changes.  The  chief  value  of  the  blood  examination,  how- 
ever, in  syphilis  is  not  for  diagnosis  but  as  a  measure  of  the 
stage  and  severity  of  the  infection.  Low  haemoglobin  and  high 
percentages  of  the  lymphocytes  are  characteristic  of  severe 
types.  Leucocytosis  usually  means  that  the  case  has  got  be- 
yond the  primary  stage,  while  in  the  tertiary  stage  the  presence 
of  myelocytes  with  a  marked  anaemia  is  of  serious  import. 

Certain  cases  of  this  last  type  may  closely  resemble  per- 
nicious anaemia,  from  which,  however,  they  are  to  be  distin- 
guished by  their  low  color  index,  the  frequent  presence  of  leu- 
cocytosis,  and  the  relative  infrequency  of  megaloblasts  as 
compared  with  the  normoblasts,  in  case  nucleated  red  cells  are 
present. 

LEPROSY. 

Winiarski  (Petersburger  medicinische  Wochenschrift,  1892, 
page  365)  gives  a  careful  study  of  seventeen  cases  of  leprosy, 
and  P.  K.  Brown1  has  watched  sixteen  cases.  They  find  in 
young  persons  with  mild  cases  no  changes  from  the  normal 
blood. 

In  severe  cases,  especially  in  old  people,  the  anaemia  may  be 
severe  (2,290,000  red  cells  with  fifty-four  per  cent  of  haemoglo- 
bin) and  even  comparable  to  pernicious  anaemia  (1,989,000  red 
cells  with  sixty -three  per  cent  of  haemoglobin).  In  anaemic 
cases  the  color  index  is  apt  to  be  high,  in  one  case  1.7  (!). 
Such  severe  types  are  associated  with  an  increase  of  the  average 
diameter  of  the  red  cells  which  explains  the  high  color  index. 
The  haemoglobin  was  not  relatively  low  in  any  case. 

Leucocytes. 

No  increase  was  present  in  any  case.  Four  cases  were  sub- 
normal. The  percentage  of  lymphocytes,  as  in  other  debilitated 
conditions,  is  often  high  (forty-five  to  forty -seven  per  cent). 

Bacteriology  of  the  Blood. 

Brown  has  succeeded  in  demonstrating  the  leprosy  bacillus 
in  the  blood  of  one-half  of  his  cases.  The  bacilli  appear  for  the 

1  San  Francisco  County  Medical  Society,  July  13th,  1897. 


LEPROSY.  273 

most  part  within  the  leucocytes,  and  here  they  accumulate  in 
large  numbers.  It  is  especially  in  the  tubercular  form  of  the 
disease  that  Brown  has  found  them.  He  was  unable  to  cultivate 
the  bacillus. 

Streker  '  has  likewise  found  the  bacillus  in  the  blood  of  four 
cases. 

1  Munch,  med.  Woch. ,  1897,  Nos.  39,  40. 
18 


PART  IV. 

DISEASES  OP  SPECIAL  ORGANS. 


CHAPTEE  VII. 

DISEASES    OF    THE    DIGESTIVE    APPARATUS. 

1.  Mouth. 

In  a  case  of  thrush  complicating  chronic  nephritis  the 
following  counts  were  recently  recorded  at  the  Massachusetts 
Hospital:  October  16th— Eed  cells,  5,000,000;  white  cells, 
16,200;  haemoglobin,  52  per  cent.  October  24th— White  cells, 
13,800;  haemoglobin,  55  per  cent. 

2.  (Esophagus  (see  Malignant  Disease,  page  345) . 

3.  Stomach. 

The  conditions  existing  in  the  stomach  may  influence  the 
blood  profoundly  in  three  ways : 

(a)  They  may  be  such  as  to  prevent  the  normal  absorption  of 
nitrogenous  material  on  which  the  blood,  like  all  tissues,  is  ab- 
solutely dependent.      Then  the  blood  becomes  starved.     The 
extreme  of   this  condition  is  the  so-called   "atrophy  of  the 
gastric  tubules"  which  may  produce  a  fatal  anaemia.    In  lesser 
degrees  the  same  process  is  at  work  in  many  forms  of  chronic 
dyspepsia,  gastritis,  or  chronic  starvation. 

(b)  They  may  lead 'to  severe  and  repeated  hemorrhages. 

(c)  They  may  lead  to  an  auto-intoxication  which  poisons  the 
blood  as  well  as  other  tissues. 

On  the  other  hand,  it  is  probably  through  the  influence  of  an 
altered  blood  serum  on  the  duodenal  mucous  membranes  that 
ulcer  of  the  duodenum  is  a  sequel  to  severe  burns  of  the  surface 
of  the  body. 

For  an  account  of  the  influence  on  the  blood  of  digestion, 
ingestion  of  liquid,  and  starvation,  see  page  99. 


GASTRIC    ULCER.  275 

DISEASES     OF    THE     STOMACH. 

ANOREXIA  NERVOSA. 

From  pure  starvation  the  red  cells  may  get  as  low  as  900,000 
as  in  the  case  mentioned  by  Martin.  In  the  early  stages  the 
blood  is  normal.  A  recent  hospital  case  showed  8,900  leucocytes 
with  87  per  cent  of  haemoglobin. 

GASTRIC   CANCER. 
(See  Malignant  Disease,  page  333.) 

GASTRIC  ULCER. 
Eed   Cells  and  Haemoglobin. 

A  severe  anaemia  is  common.  Out  of  the  28  cases  in  Table 
XXV.,  13,  or  nearly  one-half,  had  less  than  50  per  cent  of  haemo- 
globin, and  of  the  21  in  which  the  red  cells  were  counted,  5  had 
under  3,000,000  red  cells  per  cubic  millimetre.  The  average 
count  of  red  cells  at  the  time  when  treatment  began  was  3,800,- 
000.  There  is  no  single  disease,  so  far  as  I  am  aware,  in  which 
the  red  cells  are  so  apt  to  be  so  low,  except  pernicious  anae- 
mia. Even  cancer,  as  a  rule,  does  not  fall  so  low.  This  is  due 
mostly,  I  think,  to  the  frequency  of  hemorrhage  from  the  ulcer ; 
it  is  uncommon  to  see  marked  anaemia  in  patients  who  had 
never  had  a  hemorrhage. 

This  anaemia  is  all  the  more  striking  when  we  remember  that 
the  frequent  vomiting  from  which  most  patients  suffer  tends  to 
concentrate  the  blood,  increase  the  number  of  cells  in  a  drop  and 
so  to  make  the  blood  seem  less  anaemic  than  it  really  is.  This 
tendency  to  concentration  is  probably  effective  in  some  of  the 
cases  observed  especially  by  Oppenheimer, '  in  which  de- 
spite great  pallor  he  found  normal  counts  of  red  cells  and 
haemoglobin. 

It  is  in  such  cases  that  the  estimation  of  the  dry  residue  of  the 
blood  serum  would  be  of  real  value  could  it  be  made  short  and  simple 
enough  for  clinical  work.  Grawitz,  who  is  the  prophet  of  this  branch  of 
blood  examination,  gives  an  interesting  case  illustrating  this  point. 

A  girl  of  twenty-five,  suffering  with  peptic  ulcer,   and  exceedingly 

1  Deut.  med.  Woch.,  1889,  No.  42. 


276 


SPECIAL    PATHOLOGY   OF   THE   BLOOD. 


pale,  showed  on  counting  the  corpuscles  4, 140,  000  per  cubic  millimetre  (no 
considerable  reduction),  and  ninety  per  cent  of  haemoglobin.  A  second 
count  showed  4, 340, 000  corpuscles  and  ninety-one  per  cent  of  haemoglobin. 
But  the  dry  residue  of  the  serum  was  reduced  to  three-fourths  its  normal 
amount.  The  serum  suffers  in  anaemia  as  much  as  the  corpuscles  do. 
Any  influence  which  deprived  the  serum  of  one-fourth  of  its  normal  solids 
(oedema  being  absent)  must  have  really  affected  the  corpuscles  very  much. 
Therefore  the  corpuscles  must  actually  have  been  reduced  to  about  3, 800, 000, 
the  reduction  being  masked  by  the  concentration  of  the  blood  from  vomit- 
ing. Lymph  cannot  have  run  into  the  vessels  and  diluted  the  serum,  for 
(owing  to  the  vomiting)  the  tide  is  all  the  other  way.  If  then  the  serum  is 
reduced  a  quarter  the  corpuscles  must  be  so  likewise.  Unfortunately,  to  test 
the  dry  residue  of  the  blood  serum  requires  more  time,  skill,  and  apparatus 
than  clinicians  are  apt  to  have.  It  is  yaluable  whenever  we  wish  to  know 
whether  or  not  an  anaemia  is  being  masked  by  concentration  of  the  blood. 

In  severe  cases  the  usual  qualitative  evidences  of  secondary 
anaemia  (deformities,  scanty  normoblasts)  are  to  be  found. 

TABLE  XXV.,  A. — GASTRIC  ULCER  WITH  HEMORRHAGE. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

23 

F. 

1,672,000 

6,000 

40 

One  pint  of  blood  vomited  on  pre- 

vious day  ;    blood  in   stools  ;  re- 

covery. 

29 

F. 

1,676,000 

14,  750 

36 

Large  hemorrhage  ;  recovery. 

25 

F. 

1,750,000 

4,000 

, 

Recovery. 

24 

F. 

1,892,000 

7,000 

30 

January  16th,  after  hemorrhage. 

2,304,000 

.... 

27 

January  22d. 

3,  064,  000 

3,500 

35 

January  31st. 

3,920,000 

48 

February  10th. 

4,680,000 

55 

February  20th. 

63 

February  28th. 

67 

March  5th. 

29 

F. 

1,972,000 

4,000 

38 

Recovery. 

52 

F. 

2,031,000 

17,200 

30 

Hemorrhage  and  perforation. 

42 

F. 

2,216,000 

13,500 

32 

26 

F. 

2,968,000 

5,300 

45 

November  9th,  exclusive  rectal  feed- 

ing till  17th. 

2,788,000 

30 

November  16th. 

34 

November  21st. 

2,296,000 

34 

November  29th. 

3,208,000 

40 

December  3d. 

30 

F. 

3,432,000 

7,820 

45 

Hemorrhage  previous  day. 

4,222,000 

10.600 

75 

Two  weeks  later. 

4,392,000 

6^700 

70 

Three  weeks  later. 

25 

F. 

3,664,000 

14,  700 

45 

48 

F. 

4,900,000 

6,200 

40 

GASTRIC    ULCER. 


277 


TABLE  XXV.,  B. — GASTRIC  ULCER  WITHOUT  HEMORRHAGE. 


Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

19 
21 

F. 
F. 

5,856,000 
5,100,000 

10,  650 

90 

70 

40 
39 

F. 
F 

4,400,000 

9,000 
11  100 

53 

68 

23 

F 

9  300 

90 

22 

F. 

8  300 

75 

30 

F. 

6  800 

70 

25 

F. 

6,550 

85 

35 

F. 

6,500 

50  April  27th 

47 

F. 

6  300 

45  June  6th. 

57 

38 

F. 

5  800 

60 

19 
20 

F. 
F. 

5,600 
4,300 

68 

57 

Haemoglobin. 

As  a  rule  the  color  index  is  low.  Only  one  examination  in 
the  cases  of  the  Massachusetts  Hospital  series  showed  an  in- 
creased amount  of  haemoglobin  per  corpuscle,  and  as  this  was 
not  repeated  or  verified,  it  may  have  been  a  mistake.  In  all  the 
other  thirty  examinations  the  color  index  was  low  (e.g.,  Case  5, 
color  index  =  .39). 

Yet  Osterspey  records  1,900,000  red  cells  with  31  per  cent 
of  haemoglobin  (color  index  =  .81) ;  3,296,000  with  70  per  cent 
haemoglobin  (color  index  =  1.09);  4,048,000  with  84  per  cent 
haemoglobin  (color  index  =  1.05).  Such  cases  are  certainly 
rare. 


White  Cells. 

Leucocytosis  is  practically  never  seen  except  after  hemor- 
rhage and  during  digestion.  When  patients  who  have  been  fed 
for  some  time  by  the  rectum  are  first  given  food  by  the  mouth, 
the  digestion  leucocytosis  may  be  very  great,  as  in  Case  11  of  the 
above  series,  in  which  the  cells  increased  from  4,000  to  15,500! 
The  presence  of  a  leucocytosis,  when  the  influence  of  bleeding 
and  digestion  are  excluded,  is  against  the  diagnosis  of  ulcer  of 
the  stomach. 


278 


SPECIAL   PATHOLOGY    OF   THE   BLOOD. 


DUODENAL  ULCER. 


Age. 

I 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

30 

47 

M. 
M. 

3,776,000 
2,100,000 

2,480,000 
2,630,000 

Normal 
12,000 
7,650 
11,600 
11,000 
6,000 
6,500 

50 
35 

July  24th,  much  coffee  groiyids. 
July  29th  (five  days  fasting). 
Four  hours  after  meals. 
Constant  feeding,  July  30th. 
August  8th. 
August  21st,  operation. 

38 
36 

These  figures  are  given  simply  to  show  that  the  blood  in 
duodenal  ulcer  undergoes  much  the  same  changes  as  in  gastric 
ulcer,  and  need  no  further  comment. 


ACUTE  GASTRITIS  AND  DYSPEPSIA. 

Acute  gastritis  or  gastro-enteric  attacks  (Hay em's  "embarras 
gastrique")  do  not  affect  the  red  cells  or  haemoglobin,  but  are 
very  often  accompanied  by  leucocytosis  (see  Tables  XXVI.,  A 

TABLE  XXVI.,  A.— ACUTE  G ASTRO-ENTERITIS. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

31 
8 
50 

M. 
F. 
F 

7,000,000 
4,800,000 

18,000 
17,800 
15,100 

'SO' 
70 

Temperature  104°.     Well  next  day. 
Temperature  101°. 

13 

98 

F. 
M 

5,184,000 

15,000 
14  400 

85 

Well  next  day. 
September  17th   temperature  103° 

30 
90 

F. 
M 

4,860,000 

12,800 
9,100 
14,200 
12,000 

'so' 

67 

September  18th. 
September  21st,  temperature  normal. 
Well  in  three  days. 

36 

F 

11,600 

68 

23 
17 
29 

F. 
F. 
F 

6,244,000 
4,600,000 

11,600 
11,000 
11,000 

86 
70 

Well  in  two  days. 
Temperature  101°. 

70 
37 

28 

F. 
M. 

M 

4,632,000 
4,186,000 

10,000 
9,200 
6,900 

90 

68 
90 

Temperature  102°. 

23 

57 
23 
39 

F. 
F. 
F. 
F 

3,860,000 

5,  144,  bob 

6,400 
6,000 
5,400 
5,200 

65 

'95' 
50 

Temperature  101°. 
Temperature  100°. 

CHRONIC    GASTRITIS. 


270 


and  (B).  Where  this  is  the  case,  it  may  help  us  to  exclude 
typhoid  fever,  which  has  no  leucocytosis.  Even  a  twenty-four 
hours'  dyspeptic  attack  may  increase  the  leucocytes  notably,  as  in 
Cases  1  and  2  in  Table  XX YL,  A,  and  the  presence  of  such  an  in- 
crease need  not  make  us  suspect  anything  behind  the  dyspepsia. 
It  is  probably  to  be  classed  as  a  toxic  leucocytosis  due  to  ab- 
sorption of  morbid  products  from  stomach  or  intestine.  Fibrin 
may  be  increased  during  the  period  of  leucocytosis. 

TABLE  XXVI.,  B — DYSPEPSIA  AND  GASTRITIS. 


g 

Age. 

I 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

24 

M. 

6,  280,  000 

22,  700 

Gastralgia  *  constipation  *  whole 

belly  tender. 

12,800 

Three  days  later  ;  well  in  a  week. 

2 

27 

F. 

4,750,000 

14,000 

74 

At  mealtime,  11,200;  four  hours 

later,  12,150. 

3 

26 

F. 

4,920,000 

11,000 

55 

Dyspepsia. 

4 

23 

M. 



11,000 



Acute  gastritis. 

5 

5,016,000 

8,924 

86 

0 

37 

M. 

7  326 

77 

Chronic  crnsti'lc  Ccitriri*}i 

7 

30 

F. 

3,678,000 

7,000 

75 

Nervous  dyspepsia. 

f  Before    meal,    November   1st, 

8 

41 

M. 

4,524,000 

6,000 

68 

6,000;    November  2d,   6,300. 
1  After    meal,     November    1st, 

I     6,800;   November  2d,   7,400. 

9 

49 

F. 

4,200,000 

4,000 

80 

Chronic  gastritis. 

10 

11 

18 
60 

F. 
M. 

5,016,000 
3,504,000 

3,200 

2,800 

45 

50 

Dyspepsia. 
Chronic  gastritis. 

CHRONIC  GASTRITIS. 
(See  Cases  6,  9,  and  11,  Table  XXVI.,  B.) 

Here  the  conditions  are  different  and  we  never  find  an  in- 
crease of  the  white  cells,  but  often  a  decrease  due  to  malnutri- 
tion. Digestion  may  produce  no  leucocytosis,  or  the  increase 
may  be  very  slight  and  late  in  appearing  (four  to  five  hours  after 
a  meal  instead  of  two  to  three  hours).  It  wa«  present  in  nine 
out  of  twelve  cases  in  our  series. 

Anaemia  is  very  often  present  and  may  be  extreme.  It  is  be- 
lieved by  very  high  authorities  that  a  pernicious  anaemia  may  be 
caused  by  chronic  gastritis  with  atrophy  of  the  gastric  tubules. 
The  writer  has  never  had  the  good  fortune  to  see  such  cases. 


280 


SPECIAL    PATHOLOGY    OF    THE   BLOOD. 


The  practical  points  about  the  blood  of  chronic  gastritis  are : 

(a)  The  not  infrequently  severe  anaemia. 

(6)  The  not  infrequent  absence  of  digestion  leucocytosis  as  in 
gastric  cancer,  from  which  therefore  the  absence  of  digestion  leu- 
cocytosis does  not  distinguish  it. 

The  presence  of  a  leucocytosis  militates  against  the  diagno- 
sis of  chronic  gastric  catarrh,  and,  if  hemorrhage  is  excluded, 
points  toward  cancer. 


HYPERACIDITY  AND  HYPERSECRETION. 

The  leucocytes  average  higher  in  these  conditions  than  in 
chronic  gastritis  or  dyspepsia  with  normal  or  decreased  secre- 
tions (see  Table  XXVII.).  Otherwise  the  blood  is  not  re- 
markable. 

TABLE  XXVII. — HYPERACIDITY  AND  HYPERSECRETION. 


Age. 

i 

02 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

Adult. 

M. 

5,024,000 

12,  300 

82 

30 

F. 

5,768,000 

10,800 

82 

Chronic  gastritis. 

40 

M. 

5,300,000 

10,000 

85 

Slight     digestion     leucocytosis  : 

12,  270  before  meal,  14,  300  three 

hours  later. 

40 

M. 

3,340,000 

7,780 

1 

Dilated  stomach  ;    no    digestion 

leucocytosis. 

28 

F. 

4,016,000 

5,994 

76 

57 

M. 

4,160,000 

3,600 

34 

Lead     poisoning     and     dilated 

stomach. 

DILATED  STOMACH. 


I 

Age. 

'A 
£ 

Red  cells. 

White 
cells. 

Per  cent, 
haemo- 
globin. 

Remarks. 

1 

2 

8 

22 
51 
47 

F. 
M. 
M 

6,216,000 
4,184,000 
4,720,000 

10,400 
9,600 
8,000 

83 
55 

Nervous  dyspepsia. 

4 
5 

30 

64 

F. 
M. 

5,000,000 
5,264,000 

6,000 
4,600 

75 
70 

Movable  kidney. 

DILATED   STOMACH. 

In  many  cases  proteid  absorption  is  so  faulty  that  the  blood 
is  severely  starved,  but  the  ancemia  may  be  concealed  by  the  con- 


DISEASES    OF    THE    INTESTINE.  281 

centration  of  the  blood  brought  about  by  the  constant  vomiting 
of  large  amounts  of  fluid.  Kussmaul  has  shown  that  patients 
often  vomit  more  fluid  than  they  ingest,  and  it  is  obvious  what 
must  be  the  drain  of  this  process  on  the  fluids  of  the  blood  and 
all  other  tissues. 

Digestion  leucocytosis  is  often  absent,  as  in  cancer  or  chronic 
gastritis. 

CORROSIVE  GASTRITIS. 

The  blood  was  examined  in  a  case  of  this  kind  in  1895  at  the 
Massachusetts  General  Hospital  with  the  following  result :  Red 
cells,  3,792,000;  white  cells,  32,500;  haemoglobin,  fifty-three  per 
cent. 

DISEASES    OF    THE    INTESTINE. 

INFLUENCE  OF  SALINE  CATHAKTICS  ON  THE  BLOOD. 

Hay  '  gives  the  following  figures,  showing  the  effect  of  sul- 
phate of  sodium  in  concentrating  the  blood:  Healthy  man  of 
thirty -three,  3:35  P.M.  Red  corpuscles,  5,025,000;  given  85 
c.c.  of  a  concentrated  solution  of  sulphate  of  sodium  in  water; 
thirty-five  minutes  later  blood  count  showed  red  corpuscles, 
6,540,000;  sixty -five  minutes  later  blood  count  showed  red  cor- 
puscles, 6,790,000;  four  hours  later  blood  count  showed  red  cor- 
puscles, 4,930,000.  Evidently  much  fluid  was  drawn  out  of  the 
blood-vessels  and  then  within  four  hours  the  tissues  had  sup- 
plied the  loss  and  the  blood  had  returned  to  its  normal  density. 

Hay  also  showed  that  dilute  solutions  of  the  same  salt  had 
far  less  effect  in  concentrating  the  blood.  Farther  he  demon- 
strated that  if  the  blood  is  already  concentrated  when  the  saline 
is  given,  no  purgative  effect  follows. 

Grawitz  confirms  these  results;  he  found  also  that  common 
salt  still  further  concentrates  the  blood  (hence  its  production  of 
thirst),  and  considers  that  (as  this  concentration  accelerates 
coagulation}  the  household  use  of  salt  water  as  a  remedy  to  stop 
hemorrhage  is  well  founded. 

'Hay:  "The  Action  of  Saline  Cathartics."  Journal  of  Anatomy  and 
Physiology,  1882,  p.  430. 


282 


SPECIAL   PATHOLOGY    OF   THE    BLOOD. 


TABLE  XXVIII. — ENTERITIS,  COLITIS,  AND  DYSENTERY. 


0 

fc 

Age. 

y, 
3 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

45 

M. 

3,840,000 

17,000 
14,300 

50 

Chronic  dysentery.    August  26th, 
September  3d. 

7,700 

5th,d}'sentery  ceased 

8,800 

20th. 

2 

25 

F 

17  000 

Chronic  entero-colitis 

8 

4 

Adult. 
Adult. 

M. 
M 

3,624,000 
4  320  000 

13,000 
12  400 

58 

Chronic  entero-colitis. 
Ulcerative  colitis 

2  732,000 

10  600 

Two  weeks  later. 

4,  488,  000 

6,000 

Three    weeks    later  ;    much  im- 

5 

6 

39 
3 

F. 
F 

6,776,000 
4,800,000 

8,900 
7,900 

100 

proved. 
Acute  febrile  dysentery  ;  bloody 
movements  every  hour. 
Ulcerative  colitis. 

7 
8 

Adult. 

27 

M 
M 

4,100,000 
4,872,000 

7,560 
7,000 

72 

Chronic  enteritis. 
"         diarrhoea  and  tetany. 

9 
10 
11 

20 
26 
65 

M. 
M. 
M 

5,008,000 
4,900,000 

6.460 
5,300 
5  200 

39 

80 
80 

diarrhoea  (tubercular?). 
Bloody  stools  ten  days. 
Catarrhal  entero-colitis 

12 
13 
14 

40 

27 
34 

F. 
F. 
F. 

2,996,000 
4,500,000 
3,920,000 

5,000 
5,000 
4,200 

37 

70 
71 

Chronic  colitis. 
Diarrhoea. 
Chronic  colitis. 

ACUTE  ENTERITIS. 

Practically  the  great  majority  of  cases  of  acute  enteritis  are 
part  of  a  gastro-enteric  attack,  and  in  Table  XXVI.  (see  page 
278)  the  two  have  been  lumped  together.  What  was  said  of  that 
table  (page  279)  need  not  be  here  repeated.  Besides  the  slight 
leucocytosis  there  mentioned,  we  may  find  in  cases  in  which  the 
stools  are  very  watery,  a  temporary  concentration  of  the  blood 
with  increased  specific  gravity  and  red  corpuscles. 


CHRONIC  DIARRHCEA. 
(See  Table  XXVHI.) 

In  acute  diarrhoea  the  other  tissues  respond  to  meet  the  loss 
of  fluid  sustained  by  the  blood,  and  the  blood  is  soon  normal 
again.  But  when  this  process  goes  on  long,  the  body  becomes 
so  wasted  that  the  blood  must  share  in  the  starvation  and  tlu> 
albuminoids  are  drained  out  of  it,  leaving  it  watery  and  poor  in 
corpuscles.  A  patient  of  Grawitz  after  years  of  chronic  dysen- 


INTESTINAL    OBSTRUCTION. 


283 


tery  had  but  1,880,000  red  cells  per  cubic  millimetre,  while  the 
serum  had  twice  the  normal  amount  of  water  and  half  the  normal 
amount  of  solids.  I  have  seen  the  count  fall  as  low  as  1,928,000 
in  a  case  of  prolonged  colitis,  with  final  recovery.  In  another 
case  the  red  cells  reached  no  lower  than  2,440,000,  but  the 
haemoglobin  was  but  ten  per  cent.  A  differential  count  of  this 
man's  blood  showed  the  following: 

Polymorphonuclear  neutrophiles 66.3  per  cent. 

Lymphocytes  (small) 24.9        " 

Lymphocytes  (large)  ...    6.0 

Eosinophiles 1.4        " 

Myelocytes , 1.4        " 

While  counting  400  leucocytes  I  saw  8  normoblasts  and  5 
megaloblasts.  The  total  leucocyte  count  was  9,800  per  cubic 
millimetre. 

Cases  1,  3,  4,  12,  and  14  of  the  series  in  Table  XXVIII. 
show  similar  conditions.  The  haemoglobin,  however,  usually 
suffers  most,  and  the  color  index  is  low. 

Leucocytosis  is  rare,  but  does  occasionally  occur,  possibly 
owing  to  some  complication  or  auto-intoxication. 

TABLE  XXIX. — INTESTINAL  OBSTRUCTION. 


Age. 

g 

02 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

3  120  000 

20  800 

Cancer 

52 

M 

5  568  000 

18  860 

9th  of  May  cancer 

Adult. 

M 

18,800 
14,666 



17th  of  May,  cancer. 
No  fseces  three  days. 

12  400 

No  urine  two  days. 
One  day  later    no  fseces  *  urine 

4  100 

drawn  by  catheter. 
Three  days  later    bowels  moved 

35 

M 

3,  504  000 

12,000 

six  times. 
Chronic  obstruction  with  hemor 

21 

M 

5  150  000 

12  000 

rhage. 
Obstruction  (hv  *\  h^ncH 

56 

57 
Adult. 
72 
Adult. 

M 

F. 
F. 
M. 
M. 
M. 
M. 

4,440,000 
4,272,000 
5,800,000 
4,850,000 
5,200,000 
5,540,000 

12,000 
11,000 
6,800 
6,000 
4,000 
4,000 

52 

75 

Cancer. 
Cancer. 

Cholera  is  discussed  on  page  211. 
For  appendicitis  see  Abscess,  page  222. 


284 


SPECIAL   PATHOLOGY   OF    THE   BLOOD. 


INTESTINAL  OBSTRUCTION. 

The  only  point  brought  out  by  Table  XXIX.  is  that  the 
white  cells  may  be  increased,  especially  where  the  obstruction  is 
cancerous.  Hence  the  blood  count  cannot  be  relied  on  to  help 
us  in  the  diagnosis  between  obstruction  and  peritonitis.  It  is 
more  likely  that  the  examination  of  the  amount  of  fibrin  will  be 
useful,  as  it  is  said  to  be  increased  in  peritonitis  and  not  in  ob- 
struction. 

DISEASES     OF     THE     LIVER. 
CATARRHAL  JAUNDICE. 

The  serum  is  colored  yellow  or  greenish-yellow  and  contains 
bile  pigments  in  solution.  It  has  been  asserted  that  jaun- 
dice can  be  recognized  here  before  it  shows  in  the  skin  or 
urine.  In  mild  cases,  i.e.,  where  some  bile  goes  to  the  intes- 
tine and  the  obstruction  is  not  long  standing,  the  blood  is 
practically  normal,  as  the  cases  in  Table  XXX.  show.  No 

TABLE  XXX. —CATARRHAL  JAUNDICE. 


Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent  haemoglobin. 

21 

M. 

10.500 

81 

44 

M. 

10,200 

25 

30 
42 
26 

21 
30 

F. 

F. 
M. 
M. 
M. 
M. 

4,310,000 

2,896,666 
4,800.666 

10,  000 
10,000 
8,000 
9,600 
8,775 
7,500 
7,500 
7,400 

77 
90 

68 
47.    Alcoholic  gastritis. 

65 

64 

30 
53 

29 

M. 

M. 
M 

4,240,666 

7.300 
6,793 
6,200 

79 

82 

35 
29 

19 

M. 
M. 
F. 

F 

4,996,000 
4,350,000 

6,000 
4,900 
4,200 
9,600 
4,000 

78 
85 
85 

one  of  these  cases  shows  any  leucocytosis,  and  the  red  cells 
and  haemoglobin  have  not  suffered  except  in  the  alcoholic  case 
in  which  other  causes  for  anaemia  were  present.  This  is  con- 


DISEASES   OF   THE   LIVER.  285 

trary  to  the  observations  of  Grawitz,  who  found  constantly 
leucocytosis,  but  agrees  with  those  of  v.  Limbeck  and  Hay  em, 
who  never  found  any  increase  of  leucocytes  or  any  other  changes 
in  the  blood  count.  Coagulation  and  the  amount  of  fibrin  are 
normal.  Yon  Limbeck  noticed  an  increased  resistance  of  the  red 
cells  to  the  influence  of  distilled  water  and  dilute  saline  solu- 
tions which  in  normal  blood  dissolve  the  haemoglobin.  He 
noticed  also  that  the  size  of  the  red  corpuscles  was  greater  than 
normal,  their  volume  in  a  given  amount  of  blood  being  seventy- 
seven  to  eighty-one  per  cent  (i.e.,  they  take  up  seventy -seven  to 
eighty-one  per  cent  of  the  room  occupied  by  the  drop)  while  the 
normal  is  about  forty-four  per  cent.  This,  was  in  cases  with 
only  from  4,000,000  to  5,200,000  red  cells  per  cubic  millimetre, 
so  that  it  was  evidently  due  not  to  an  overcrowding  of  the  drop 
with  red  cells  but  to  a  true  increase  of  size  in  the  individual 
cells.  The  same  fact  has  been  attested  from  a  different  point  of 
view  by  the  investigations  of  v.  Noorden,  who  found  the  solid 
residue  increased,  and  of  Hammerschlag ;  and  Grawitz  has  noted 
an  increase  in  the  specific  gravity  of  the  whole  blood,  though 
that  of  the  serum  remained  normal.  Normal  red  corpuscles  put 
into  the  serum  of  icteric  patients  increase  their  diameter  con- 
siderably, so  that  apparently  the  serum  is  responsible  for  the 
change. 

Qualitative  Changes. 

Grawitz  noted  in  severe  cases  that  crenation  took  place  much 
more  rapidly  than  usual  in  freshly  drawn  blood,  and  that  the 
rouleaux  formation  did  not  take  place.  This  latter  point  was  also 
noticed  by  Hofmeier '  in  icterus  of  the  new-born.  Silbermann 2 
noticed  in  the  same  disease  great  deformities  in  the  size  and 
shape  of  the  cells.  In  severe  febrile  icterus  Weintraud  noted 
in  the  red  cells  the  white  spots  and  streaks  with  active  (molec- 
ular) movements  described  by  Maragliano  (see  page  87)  as  en- 
doglobular  degenerative  changes. 

Summary. 

Normal  blood,  except  for  increased  size  of  the  red  cells  and 
some  degenerative  changes  in  severe  cases. 

1  "Die  Gelbsucht  der  Neugeborenen,"  Stuttgart,  1882. 

2  "Die  Gelbsucht  der  Neugeborenen."    Arch.    f.  Kinderheilk. ,  1887, 
p.  401. 


286  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

Diagnostic  Value. 

The  constant  presence  of  leucocytosis  excludes  an  uncom- 
plicated "  catarrhal"  jaundice,  and  points  to  the  probability  of 
malignant  disease  or  inflammation  (cholangitis,  abscess).  Syph- 
ilis and  cirrhosis  of  the  liver  might  show  the  same  condition  of 
the  blood  unless  the  characteristics  of  syphilitic  blood  were  very 
marked  (see  page  269).  From  a  severe  cholaemia  the  absence  of 
any  marked  anaemia  distinguishes  a  purely  catarrhal  case.  (For 
the  changes  in  cholsemia  see  page  290.) 

CIRRHOSIS  OF  THE  LIVER. 

1.  ORDINARY  (ATROPHIC)  CIRRHOSIS  WITHOUT  JAUNDICE. 

In  the  early  stages  (according  to  Hay  em)  neither  the  red  cells 
nor  the  haemoglobin  fall  considerably.  Most  other  observers 
(perhaps  thinking  chiefly  of  the  later  stages)  report  marked 
anaemia.  Wlajew1  counted  from  3,000,000  to  4,000,000  red  cells ; 
v.  Limbeck  had  a  case  with  only  1,500,000.  He  noted  that  the 
count  might  be  increased  after  a  tapping  in  cases  with  ascites, 
owing  to  the  concentration  of  the  blood  from  the  rapid  refilling 
of  the  belly  with  serum.  Grawitz,  on  the  other  hand,  noticed 
precisely  the  opposite  effect  in  a  case  whose  blood  before  tap- 
ping had  been  concentrated  by  cyanosis,  the  heart's  action  being 
embarrassed  by  the  ascites.  After  tapping,  when  the  heart's 
action  had  become  easier  and  stronger,  the  cyanosis  disappeared 
and  the  blood  count  fell  from  4,700,000  to  4,300,000.  In  v.  Lim- 
beck's case  it  rose  from  4,680,000  to  5,160,000.  The  moral  is 
that  we  should  draw  no  inferences  from  the  count  of  red  cells 
soon  after  a  tapping. 

The  fifty -two  cases  in  Table  XXXI.,  A.,  were  all  advanced 
and  their  red  cells  averaged  only  3,580,000  +  per  cubic  milli- 
metre. They  steadily  decrease  as  the  disease  progresses,  one 
case  getting  as  low  as  1,300,000;  but  the  anaemia  may  be  con- 
cealed by  cyanosis  and  concentration. 

Qualitative  Changes. 

Hay  em  noticed  a  curious  stickiness  of  the  red  corpuscles,  a 
great  tendency  to  adhere  to  each  other.  Yon  Limbeck  looked 

1  Ref.  in  Petersburger  med.  Woch..  1894.  No.  43 


CIRRHOSIS   OF   THE   LIVER. 


28-7 


for  it,  but  could  never  find  it.  Hay  em  and  Maragliano  noticed 
degenerative  endoglobular  changes  in  the  red  cells  ("  etat  cribri- 
forme"). 

TABLE  XXXI.,  A.— CIRRHOTIC  LIVER  WITHOUT  JAUNDICE. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent, 
haemo- 
globin. 

Remarks. 

53 

F. 

2,950,000 

16,000 

Recent  hemorrhage. 

41 

M. 

4,300,000 

12,750 

55 

Liver  enlarged  ;  ascites. 

48 

M. 

4,992,000 

9,000 

62 

Recent  hemorrhage. 

53 

M. 

2,120,000 

9,000 

23 

March  15th. 

1,300,000 

7,500 

22 

April    8th. 

15 

April  18th. 

15 

April  29th. 

2,350,000 

6,000 

20 

May  10th. 

2,375.000 

5,300 

26 

May  12th. 

2,450,000 

5,200 

20 

June  10th. 

4,  500,  000 

7,800 

25 

June  16th. 

50 

M. 

3,440,000 

8,320 

46 

Liver  enlarged. 

34 

M. 



7,900 

95 

56 

M. 

7,500 

68 

53 

M. 

6,  200 

60 

38 

F. 

5,700 

65 

5,720,000 

5,200 

46 

Differential  count  normal. 

54 

M. 

5,400 

64 

56 

M. 

4,680,000 

5,000 

48 

Liver  atrophic,  July  12th. 

4,312,000 

4,000 

62 

Julv  25th. 

42 

M. 

2,920,000 

4,500 

56 

October  30th. 

13,400 
15,300 

November  7th,  during  digestion. 
November  llth,  during  digestion. 

53 

M. 

3,800 

72 

54 

F. 

3,300 

65 

63 

M. 

3,  844',  GOO 

3,000 

50 

M. 

3,568,000 

2,400 

50 

52 

M. 

3,440,000 

2,400 

50 

Hemoglobin. 

Usually  the  color  index  is  low;  the  average  was  .66  in  the 
ten  Massachusetts  Hospital  cases. 

White  Cells. 

Except  after  recent  hemorrhage  none  of  our  cases  showed  any 
leucocytosis,  and  the  average  count  was  7,240,  some  cases  hav- 
ing notably  low  figures  (2,400,  3,000,  4,500). 

Hay  em's  results  agree  with  this.  Yon  Limbeck  makes  no 
definite  statement  on  this  point.  Eosenstein  and  Wlajew  found 
leucocytosis,  the  latter  12,000  to  17,000.  Possibly  their  cases 


288 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


include  the  forms  of  cirrhosis  with  jaundice  in  which  (see  Table 
XXXI.,  B)  the  white  cells  are  more  often  increased. 

The  forms  of  hypertrophic  cirrhosis  without  jaundice  (fatty 
infiltrated  liver)  are  here  classed  with  the  atrophic  cases  whose 
blood  has  just  been  described. 

TABLE  XXXI.,  B.— CIRRHOTIC  LIVER  WITH  JAUNDICE. 


0 

& 

Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

2 
3 
4 
5 

42 

38 
45 
35 

57 

M. 
M. 
M. 
M. 
F 

1,024,000 
3,400,000 
4,568,000 
5,016,000 

19,  600 
19,500 
14,000 
12,000 

36 
50 
65 

Autopsy. 

Liver  enlarged. 
Liver  enlarged. 
Adult   cells    83  per  cent  *  young 

6 

7 

36 
50 

M. 
M. 

2,064,000 
2,904,000 

4,300 
2,400 

50 
54 

cells,  17  per  cent. 
Jaundice  only  transient. 
Autopsy  (hypertrophic  cirrhosis). 

2.  HYPEETEOPHIC  CIEEHOSIS  WITH  JAUNDICE. 
Red  Cells. 

True  (biliary)  hypertrophic  cirrhosis  witli  jaundice  has  ac- 
cording to  Hayem  an  intense  anaemia  in  many  cases.  In  othe1  ^ 
it  has  no  more  effect  on  the  blood  than  ordinary  atrophic  cir- 
rhosis. The  six  cases  in  Table  XXXI.,  B,  averaged  a  little  lower 
in  the  count  of  white  cells  than  the  ten  atrophic  cases,  3,200,000 
as  contrasted  with  3,580,000. 

Hcemoglobin. 

In  a  single  case  of  this  variety  of  cirrhosis  Hayem  found  in 
four  successive  blood  examinations  a  color  index  of  more  than  1. 
His  counts  are  as  follows : 


Date. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

Color  index. 

January 

9th  

1  599  600 

41 

1  27 

u 

llth    

1  884  000 

21,803 

50 

1.39 

u 

12th  

1  798  000 

18,082 

50 

1.46 

It 

15th  

1,971,000 

15,500 

53 

1.40 

Dried  specimens  showed  an  increased  average  diameter  of 
the  cells  as  in  pernicious  anaemia.  The  patient  died  January 
15th  and  the  autopsy  confirmed  the  diagnosis  of  hypertrophic 
cirrhosis. 


ACUTE   YELLOW    ATROPHY   OF   THE   LIVER.  289 

The  observations  of  v.  Limbeck  of  the  increased  volume  of 
the  red  cells  in  jaundice  may  perhaps  be  another  example  of 
the  condition  here  noted  by  Hayem.  The  presence  of  bile  in 
the  blood  makes  all  haemoglobin  estimations  unsatisfactory. 

Only  one  of  our  six  cases  showed  this  same  condition — Case 
5  in  Table  XXXI.,  B.  The  corpuscles  numbered  2,064,000,  or 
forty  per  cent,  and  the  haemoglobin  fifty  per  cent,  a  color  index 
of  1.25.  This  case  was  jaundiced  at  the  time  of  the  exami- 
nation. 

I  have  seen  no  confirmation  of  Hay  em's  observation  by  any 
other  writer. 

White  Cells. 

Leucocytosis  is  commoner  in  this  than  in  the  other  variety 
of  cirrhosis.  Hanot  and  Mennier  found  from  9,000  to  21,800 
leucocytes  per  cubic  millimetre  in  five  cases  of  hypertrophic 
cirrhosis  and  an  average  of  6,600  in  ordinary  cirrhosis.  Leu- 
cocytosis was  present  in  four  of  the  six  cases  of  the  Massachu- 
setts Hospital  series,  the  average  of  all  six  being  9,000. 

Diagnostic  Value. 

The  blood  of  either  form  of  cirrhosis  has  no  diagnostic  value, 
so  far  as  I  know,  except  to  exclude  abscess  and  hydatids.  If  no 
leucocytosis  is  present,  abscess  and  hydatid  cyst  can  usually  be 
excluded. 

HYDATID  CYST  OF  THE  LIVER. 

The  only  observations  which  I  have  met  with  are  those  of 
Hayem  and  Neusser.  Hayem  states  that  the  blood  shows  leu- 
cocytosis and  increased  fibrin.  Neusser  considers  that  the  in- 
crease of  eosinophiles  which  he  finds  in  hydatids  serves  to  dis- 
tinguish them  from  hydronephrosis,  dilated  gall-bladder,  etc. 

ACUTE  YELLOW  ATROPHY  OF  THE  LIVER. 

Grawitz  records  a  case  with  5,150,000  red  cells  and  16,000 
white  cells. 

A  single  case  with  autopsy  was  studied  at  the  Massachusetts 
General  Hospital  in  1894,  the  blood  showing  5,520,000  red  cells, 
12,000  white  cells,  and  sixty  per  cent  of  haemoglobin. 
19 


290  SPECIAL    PATHOLOGY   OF   THE   BLOOD. 

PHOSPHORUS  POISONING. 

Taussig,1  v.  Jaksch,'J  Badt,3  and  v.  Limbeck4  note  an  increase 
in  the  normal  number  of  red  cells  per  cubic  millimetre.  Taussig 
found  8,  650,  000  per  cubic  millimetre;  Badt,  6,400,000,  6,500,000, 
and  6,800,000  in  three  successive  cases;  v.  Limbeck,  6,500,000 
and  7,900,000.  That  this  increase  is  not  due  to  concentration 
of  the  blood  through  vomiting  of  liquid  is  proved  by  v.  Lim- 
beck's last  case,  in  which  no  vomiting  whatever  took  place. 

The  count  usually  falls  to  normal  within  a  few  days.  All 
these  changes  were  verified  in  thirty-three  cases  at  the  Stock- 
holm Hospital  in  1892  (see  Stockholm  Hospital  reports  for  1892)  . 

The  white  cells  in  v.  Limbeck's  second  case  were  increased 
to  12,500.  In  v.  Jaksch's  five  cases  the  counts  were  58,750, 
48,000,  8,000,  4,070,and  3,400. 


When  jaundice  is  intense  and  long  standing,  as  in  complete 
obstruction  of  the  bile  ducts  by  gall-stones  or  tumors,  the  blood 
is  weakened  very  notably,  and  haemoglobin  and  the  count  of 
corpuscles  fall  steadily.  Very  little  is  to  be  learned  upon  the 
subject  from  the  literature,  but  the  qualitative  changes  men- 
tioned under  catarrhal  jaundice  are  much  more  marked,  and 
leucocytosis  is  apt  to  be  present.  I  have  studied  the  blood  in  a 
case  of  fatal  chronic  jaundice  without  fever  and  for  which  at 
autopsy  no  cause  was  found.  The  leucocytes  ranged  between 
12,000  and  14,000. 

GALL-STONES. 

Netter6  and  Sittmann6  have  found  pyogenic  organisms  in 
cultures  from  the  blood  of  patients  with  gall-stones,  as  have  also 
-Gilbert  and  Girode.7 

1  Arch.  f.  experiment.  Path,  und  Pharm.,  vol.  xxx. 

2  Deut.  med.  Woch.  ,  1893,  p.  10. 
8  Dissert.,  Berlin,  1891. 

4  LOG.  cit.  ,  p.  34. 

*  Progres  Medical,  1886,  No.  46. 

6  Deut.  Arch,  f  .  klin.  Med.  ,  1894,  p.  323 

7  La  Semaine  Med.  ,  1890,  No.  58. 


CHOLANGITIS. 


291 


Of  the  22  cases  of  this  disease  examined  at  the  Massachusetts 
General  Hospital  2  were  complicated  with  cholangitis  (see  Table 
XXXII.,  A).  Excluding  these  2,  leucocytosis  was  present  in 
only  4  of  20  cases.  The  red  cells  were  low  in  2  cases  (2,800,000 
and  3,900, 000). 

The  absence  of  leucocytosis  helps  us  to  distinguish  the  dis- 
ease from  peritonitis  and  appendicitis,  and  excludes  suppurative 
cholangitis. 

TABLE  XXXII.,  A. —GALL-STONES. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

39 
30 
63 
9,9 

F. 
F. 

F. 
M 

4,768,000 
4,820,000 
4,610,000 

24,400 
20,000 
18,800 
16,  200 

Cholangitis  also. 
Cholau  gitis  .     Autopsy  . 

December  16th. 

40 
60 

F. 
F 

4,520,000 

13,200 
10,000 
13,000 
12,  500 

72 

December  18th. 
December  21st. 

Temperature,  100.5°. 

40 
49 

M. 
F. 



11,500 
10,250 
10,000 

70 
90 

Jaundice. 

47 

M 

9  800 

85 

45 
38 
25 
22 
25 
54 

F. 
F. 
F. 
M. 
F. 
F. 

5,'d72,00'o 
3,288,000 
4,900,000 

9,200 
8,900 
8,800 
8.000 
8,000 
7,600 

100 
60 

80 

Distended  gall-bladder. 
Jaundice. 
Jaundice. 

29 

57 

F. 
F 

2,844,000 

7,400 
7,400 

85 

37 

F 

7,300 

October  1st. 

58 

M. 

8,200 
6,000 

64 

October  5th. 

57 

F 

5  400 

68 

51 

24 

F. 
M. 

4,'  320,  000 

5,300 
4,000 

63 

Recurrent  pain  and  jaundice. 

CHOLANGITIS. 

Here  the  leucocytosis  is  well  marked  whenever  the  inflamma- 
tion has  got  beyond  the  catarrhal  stage  (see  Table  XXXII.,  B) 
and  helps  us  to  exclude  simple  impacted  gall-stone,  with  or  with- 
out colic.  Cancer  may  or  may  not  produce  leucocytosis,  but 
does  not  usually  increase  the  fibrin  network;  it  is  said  by  Hay  em 
that  cholangitis  does  increase  it. 


292 


SPECIAL   PATHOLOGY   OF   THE   BLOOD, 


TABLE  XXXII.,  B.— CHOLANGITIS. 


No. 

Age. 

Sex. 

Red  cells. 

White  cells. 

Remarks. 

1 
2 
3 
4 
5 

2l' 
65 

F. 
F. 
F. 
M. 
M 

4,800,000 
6,400,000 
4,960,000 
4,976,000 

50,000 
30,000 
22,000 
14,800 
14,  186 

Suppurative  cholangitis. 

Jaundice  and  cholaemia. 
Gall-stones  ;  chills. 

6 

11,000 

October  20th.     Operation  October  22d 

7 
8 

28 
34 

M. 
F. 

6,640,000 
5,592,000 
4,770,000 

9,000 
6,800 
4,400 

Abscess  of  liver. 
Catarrhal. 

Catarrhal. 

ABSCESS  OF  THE  LIVER. 

In  all  but  one  of  the  cases  seen  by  the  writer  (see  Table 
XXXIII.)  the  leucocytosis  has  been  very  marked.  I  have 
never  been  able  to  account  for  its  absence  in  that  case. 

The  blood  does  not  differ  from  that  of  cholangitis  with  sup- 
puration. From  cancer  it  may  often  be  distinguished  by  the 
absence  of  increased  fibrin  network  in  cancer,  while  it  is  always 
increased  in  suppurations. 


TABLE  XXXIII.— ABSCESS  OF  THE  LIVER. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

20 

15 
60 

98 

M. 

F. 
F. 
M 

4,533,000 

3,750,000 
4,460,000 

33,200 
48,000 
26,800 
18,000 
12,  600 

January  llth. 
January  14th.    Operation. 
Operation. 
Operation. 

33 

F 

11,000 

November  3d. 

26 

51 

M. 
F. 

2,664,000 
3,440,000 

17,  500 
19,200 
20,  600 

10,  200 
12,000 
15,000 

9,600 

33 

November  4th,  11  A.M. 
November  4th,  2  P.M. 
November  5th,  10  A.M.    Operation  ; 
autopsy. 
October  19th. 
October  20th. 
October  21st.      October  25th,    au- 
topsy ;    streptococci. 

CANCER  OF  THE  LIVER. 
(See  Malignant  Disease,  page  346.) 


ENDOCARDITIS.  293 

GUMMA  OF  THE  LIVER. 

Von  Jaksch  in  a  single  case  found  red  cells,  2,756,000;  white 
cells,  6,100. 

DISEASES    AFFECTING    THE    HEART. 

PERICARDITIS. 
(See  Inflammation  of  Serous  Membranes,  page  247.) 

ENDOCARDITIS. 

In  many  cases  of  acute  endocarditis  the  blood  shows  no 
changes.  In  others,  whatever  alterations  there  may  be  are  cov- 
ered up  by  those  involved  in  the  rheumatic  arthritis  associated 
with  the  endocarditis. 

ULCERATIVE  ENDOCARDITIS. 

In  idcerative  or  malignant  endocarditis,  we  may  find  the  signs 
of  a  pyogenic  infection  (see  page  216).  Sometimes  pyogenic 
cocci  can  be  cultivated  from  the  blood  and  if  present  may  be  of 
the  greatest  value  in  a  diagnosis  always  difficult  to  make. 

Grawitz  goes  so  far  as  to  say  that  in  doubtful  cases  repeated 
negative  results  of  cultures  from  the  blood  make  it  unlikely  that 
ulcerative  endocarditis  is  present. 

Sittmann '  considers  that  important  help  may  be  given  as  to 
the  position  of  the  primary  focus  of  infection  by  the  nature  of 
the  organism, present  in  blood  cultures — i.e.,  the  pneumococcus 
pointing  to  the  lung,  the  colon  bacillus  to  the  intestine,  etc. 

Red  Cells. 

As  in  all  forms  of  septicaemia  marked  anaemia  rapidly  de- 
velops, more  rapidly  probably  than  in  any  other  disease.  The 
haemoglobin  loses  about  equally  with  the  corpuscles,  according 
to  most  observers — that  is,  the  blood  destruction  is  so  rapid 
that  the  red  cells  do  not  get  thin  before  they  die,  as  is  usually 
the  case,  but  are  cut  off  in  the  prime  of  health. 

Further  evidence  of  rapid  blood  destruction  is  seen  in  the 
haemoglobinaemia  often  present. 

1  Loc.  cit. 


294 


SPECIAL    PATHOLOGY    OF    THE    BLOOD. 


Koscher  (loc.  cit.)  records  counts  of  4,400,000  and  2,750,000, 
both  fatal  cases.  In  one  cas&  seen  by  the  writer  the  count  was 
3,792,000  with  fifty-eight  per  cent  of  haemoglobin. 

White  Corpuscles. 
Bieder  reports  a  single  case  showing  these  variations : 

Temperature.  White  cells. 

January    2d,    1891 105°  17,000 

3d,    1891... 99°  13,700 

8th,  1891 103°  15,500 

10th,  1891 101.5°  18,000 

12th,  1891 101.5°  21,300 

18th,  1891 101°  18,800 

22d,    1891 104.5°  .  13,000 

February  llth,  patient  died. 

Pee  found  leucocytosis.  Eoscher  in  two  cases  found :  Case 
I.:  8,800  leucocytes;  patient  died  in  two  days.  Case  II. :  16,- 
800  and  12,000.  Krebs  in  one  case  found:  October  27th,  15,- 
500;  October  28th,  44,200;  the  patient  died  same  day. 

Nine  cases  were  counted  at  the  Massachusetts  Hospital  with 
the  following  results.  In  three  only  the  fresh  blood  was  ex- 
amined and  showed  marked  leucocytosis ;  in  the  others : 

ULCERATIVE  ENDOCARDITIS. 


Case. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

Remarks. 

1 

30,100 
15,800 
18,100 
25,700 
27,840 
18,  100 
22,000 
20,400 
12,  600 
14,500 
20,400 
24,000 
10,000 
8,900   ' 

5> 
51 

f 
J 

May  27th. 
May  30th. 
June  17th. 
May  22d. 
May  24th. 
May  26th. 
May  28th. 
Autopsy. 
January  13th. 
January  14th. 
January  16th. 
January  18th  ;  died. 

Autopsy. 

9 

3.. 

4 

5 

3,792,000 

6 

Practically  the  same  are  the  counts  in  the  following  cases  of 
apparently  "  benign"  endocarditis  with  fever  and  rapidly  shift- 
ing murmurs,  the  first  complicating  chorea  in  a  boy  of  thirteen, 
the  other  in  an  adult. 


MYOCARDITIS. 


295 


"  BENIGN"  ENDOCARDITIS. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemoglobin. 

Remarks. 

13 

M. 

.... 

20,600 

62 

May  26th.      Temperature   102°- 

104°. 

17,900 

May  29th. 

18,700 

May  31st. 

16,800 

June  3d. 

21,200 

June  4th. 

27,400 

June  8th. 

22,700 

June  llth. 

24,200 

June  13th. 

21,900 

June  15th. 

26,  100 

June  17th. 

26,800 

June  19th. 

17,400 

June  23d. 

28,700 

June  26th. 

21,200 

.  . 

July  2d  (outdoors). 

21,300 

... 

July  4th.     Left  the  hospital 

July  19th. 

56 

F. 

.... 

50,100 

November  24th. 

35,800 

November  27th. 

36,600 

November  30th. 

22,800 

... 

December  7th. 

Diagnostic  Value. 

(a)  Blood  cultures  should  never  be  omitted  in  cases  of  sus- 
pected malignant  endocarditis.  When  positive  they  are  of 
great  value,  (b)  In  excluding  typhoid  the  presence  of  leucocy- 
tosis  is  important.  I  saw  within  a  few  months  a  case  in  which 
several  consultants  had  made  the  diagnosis  of  typhoid,  but  in 
which  the  presence  of  marked  and  persistent  leucocytosis  and 
the  absence  of  a  typhoid  serum  reaction  convinced  me  that  the 
case  was  one  of  ulcerative  endocarditis.  This  has  since  been 
verified. 

MYOCARDITIS. 

Whenever  stasis  and  disturbance  of  the  circulation  result 
from  weakness  of  the  heart  wall,  blood  changes  identical  with 
those  described  under  Valvular  Heart  Disease  are  present. 
Otherwise  the  blood  is  normal. 


296  SPECIAL    PATHOLOGY    OF    THE    BLOOD. 

VALVULAR  HEART  DISEASE. 

Grawitz  divides  valvular  heart  disease  into  three  stages  with 
corresponding  blood  conditions : 

1.  Stage  of  full  compensation :  blood  normal. 

2.  Stage   of  acute  failure   of  compensation:   blood  diluted 
(Oertel's  "plethora  serosa"). 

3.  Stage  of  chronic  stasis  and  cyanosis :  blood  concentrated 
for  the  most  part ;  at  times  diluted  as  well. 

1.  A  valvular  lesion  per  se  has  no  effect  on  the  blood. 

2.  When  compensation  fails  and  blood  pressure  is  lowered, 
we  find  (especially  in  the  venous  blood)  that  the  fluid  from  the 
surrounding  lymph  spaces  has  made  its  way  into  the  vessels 
and  dilated  the  blood.     The  specific  gravity  falls,  red  cells  and 
haemoglobin  are  lower  than  before,  while  the  white  cells  are  un- 
altered, and  the  plasma  is  shown  to  be  more  watery  than  before 
as  well  as  of  increased  quantity  per  cubic  millimetre.     All  these 
changes  are  less  marked  in  capillary  blood,  and  hence  are  rarely 
observed. 

3.  If  the  heart  adjust  itself  partially  to  the  increased  work  it 
has  to  do,  and  to  the  chronic  passive  congestion  of  the  internal 
organs  and  at  the  periphery,  the  blood  is  concentrated,  probably 
in  part  by  transudations  into  serous  cavities  and  lymph  spaces, 
and  in  part  by  the  increased  excretion  of  moisture  by  the  lungs. 
The  specific  gravity  and  the  number  of  red  cells  are  increased, 
especially  in  the  capillaries,  and  to  a  lesser  extent  in  the  venous 
blood  (the  conditions  being  just  the  reverse  of  those  in  acute 
heart  failure,  stage  No.  2) .     This  is  the  condition  usually  found 
in  heart  disease  with  chronic  venous  stasis  (passive  congestion) . 

But  this  concentrated  condition  of  the  blood  may  be  offset 
from  time  to  time  by  fresh  weakening  of  the  heart  and  lessen- 
ing of  blood  pressure,  and  the  combination  of  the  two  conditions 
may  result  in  a  normal  blood  count. 

The  condition  of  concentrated  peripheral  blood  with  the  count 
of  red  cells  above  normal,  is  that  most  commonly  seen  in  chronic 
heart  disease  with  stasis. 

Von  Limbeck  finds  that  aortic  lesions  are  more  apt  to  show  a 
normal  or  diminished  blood  count,  while  mitral  disease  is  more 
apt  to  be  accompanied  by  the  temporary  dilutions  and  long- 
standing concentration,  above  described.  He  does  not  explain 


VALVULAR    HEART    DISEASE.  297 

the  cause  of  this.  One  of  his  patients  with  double  mitral  le- 
sion showed  a  decrease  of  1,170,000  red  cells  (from  7,500,000  to 
6,330,000)  after  exertion.  When  the  patient  was  quiet,  the  le- 
sion was  compensated;  on  exertion  compensation  temporarily 
failed,  blood  pressure  was  lowered,  and  the  blood  diluted. 

Sadler1  found  considerable  anaemia  in  three  out  of  four  cases 
of  aortic  disease,  while  only  two  of  seven  patients  with  mitral 
lesions  showed  anaemia. 

Schneider's2  results  were  similar  in  that  he  found  the  red 
cells  normal  in  the  aortic  cases  and  increased  in  the  mitral  ones. 

Hayem  found  anaemia  most  common  in  aortic  regurgitatiou, 
especially  in  young  people. 

In  the  Massachusetts  Hospital  records  out  of  twelve  cases  of 
mitral  disease  five  had  less  than  4,000,000  red  corpuscles  per 
cubic  millimetre.  Of  three  cases  of  aortic  disease  all  were  over 
4,000,000.  I  think  these  figures  simply  mean  that  the  mitral 
cases  are  more  apt  to  come  to  the  hospital  in  the  stage  of  acute 
failure  of  compensation — therefore  (see  above)  with  diluted 
blood — while  the  aortic  cases  often  come  while  compensation  is 
still  good  and  therefore  with  practically  normal  blood. 

White  Corpuscles. 

Almost  all  writers  whom  I  have  consulted  agree  that  the  leu- 
cocytes are  normal  unless  some  complication  occurs.  Yet  in 
a  certain  number  of  the  Massachusetts  Hospital  cases  mostly 
(but  not  exclusively)  those  with  cyanosis,  the  leucocytes  were 
increased,  the  counts  ranging  sometimes  as  high  as  15,000,  while 
the  red  cells  were  normal.  I  suppose  this  is  to  be  accounted  for 
by  the  fact  that  in  any  case  in  which  the  circulation  is  feeble 
and  slow,  the  white  cells  accumulate  at  the  periphery  even  more 
plentifully  than  the  red.  This  is  evidently  so  in  the  cases  of 
congenital  heart  disease  next  to  be  mentioned,  in  which  the  red 
cells  are  increased  only  about  forty  per  cent,  while  the  white 
are  often  one  hundred  per  cent  more  numerous  than  normal. 

The  apparently  normal  count  of  red  cells  in  some  of  our  cases 
was  probably  due  to  the  covering  up  of  an  anaemic  or  diluted 
condition  of  the  blood  by  concentration,  the  resultant  of  the  two 
forces  being  an  apparently  normal  count. 

1  Loc.  cit. ,  p.  33  2  Inaug.  Dissert. ,  Berlin,  1888. 


298  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

Koblank  (loc.  cit.)  gives  the  following  cases  illustrating  this 
condition : 

Red  cells.  White  cells. 

1.  Mitral  leakage 5,461,250        28,000  -f  ;  autopsy. 

2.  Aortic  leakage 4,716,600        13, 000 -j- 

This  leucocytosis  must  be  taken  into  account  in  making  in- 
ferences from  cases  whose  circulations  are  feeble,  and  no  deeper 
underlying  cause  (e.g.,  abscess,  cancer)  need  be  assumed  to  ac- 
count for  the  increase. 

(Edema  and  diuresis  have  in  themselves  little  or  no  constant 
effect  upon  the  blood,  as  a  recent  observation  of  Petrowsky's 
has  demonstrated. 


CONGENITAL  HEART  DISEASE. 

In  the  cyanosis  accompanying  this  affection  very  high  blood 
counts  are  reported.     Gibson  found : 


Case. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

1 

8  470  000 

12  000 

110 

2 

6  700  000 

12,000 

92 

Carmichael  reports,  red  cells,  8,100,000,  white  cells,  16,000, 
in  a  single  case,  and  Toeniessen  counted  8,820,000  and  7,540,000 
in  two  similar  cases.  In  one  case  entirely  without  evidence  of 
any  stasis  I  counted  8,431,000  red  cells  per  cubic  millimetre. 
How  such  cases  are  to  be  explained  I  do  not  know ;  the  ordinary 
explanation  of  concentration  of  the  blood  will  not  hold  in  cases 
in  which  no  stasis  or  lack  of  compensation  exists,  yet  the  skin 
is  blue  and  the  blood  counts  are  enormous. 

There  is  no  doubt  that  the  peripheral  capillaries  always  con- 
tain more  corpuscles  per  cubic  millimetre  than  do  the  veins. 
Numerous  reports  from  various  observers  agree  upon  this. 
Whether  this  is  on  account  of  the  loss  of  water  by  perspiration 
and  consequent  drain  of  blood  from  the  skin  capillaries  is  uncer- 
tain, but  in  congenital  heart  disease  both  capillary  and  venous 
blood  is  overcrowded  with  corpuscles  and  the  explanation  is 
difficult.  Hay  em  in  a  case  of  this  sort  reports  7,000,000  red 
cells  with  a  decrease  in  the  average  diameter. 


DISEASES   OF   THE    KIDNEYS.  299 

The  most  important  practical  deduction  from  these  data  is 
that  a  blood  count  in  a  patient  suffering  from  poorly  compen- 
sated heart  disease  has  no  value  in  determining  whether  or  not 
anaemia  is  present.  The  actual  number  of  corpuscles  in  the  body 
is  not  measured  by  the  number  contained  in  a  drop  of  periph- 
eral blood,  since  anaemia  may  be  effectually  masked  by  con- 
centration or  simulated  by  dilution. 

This  holds  good  equally  for  any  condition  involving  general 
stasis  and  cyanosis  either  from  embarrassment  of  the  heart's 
action  or  otherwise  (for  instance,  pneumonia  in  certain  stage, 
emphysema,  displacement  of  the  heart  by  serous  effusions,  or 
tumors),  or  local  stasis  of  the  part  from  which  blood  is  taken. 
Penzoldt J  noted  that  in  old  hemiplegic  cases,  the  blood  from 
the  affected  side  contained  more  corpuscles  than  that  from  the 
sound  side,  and  the  writer  has  noticed  the  same  thing  in  a  va- 
riety of  vasomotor  affections  involving  local  asphyxia. 

ANEURISM. 

As  a  rule  I  have  found  the  blood  entirely  normal,  but  in  the 
following  case  it  might  have  thrown  light  on  the  diagnosis.  A 
patient  was  recently  admitted  to  the  Massachusetts  Hospital 
with  an  acute  affection  of  the  chest,  supposed  to  be  pneumonia 
in  spite  of  the  slightness  of  the  fever  and  the  irregularity  of  the 
physical  signs.  At  autopsy  a  ruptured  aortic  aneurism  was 
found.  The  blood  count  had  showed  3,324,000  red  cells,  20,800 
white,  and  33  per  cent  haemoglobin.  The  low  percentage  of 
haemoglobin  and  red  cells  was  really  inconsistent  with  an  acute 
pneumonia  in  a  man  previously  well,  and  might  have  hinted 
strongly  toward  the  correct  diagnosis  had  attention  been  di- 
rected more  carefully  to  the  blood. 

DISEASES  OF  THE  KIDNEYS. 

Many  factors  other  than  the  disease  itself  may  influence  the 
blood  of  nephritic  cases.  For  instance,  in  scarlatinal  nephritis 
the  long-standing  leucocytosis  is  probably  due  largely  to  the 
scarlatinal  poison,  rather  than  to  the  nephritis.  The  occur- 
rence of  large  quantities  of  blood  in  the  urine  has  the  same  in- 
fluence as  any  other  hemorrhage  upon  the  blood. 

(Edema  as  such  has  apparently  very  little  effect  upon  the 

1  Berliner  klin.  Woch.,  1881,  p.  457. 


300  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

blood,  but  the  loss  of  albumin  in  the  urine  tells  both  on  the  cor- 
puscles and  on  the  serum,  thinning  both  with  consequent  lower- 
ing of  the  specific  gravity  of  the  blood. 

ACUTE   NEPHRITIS. 
1.  Red  Cells  and  Haemoglobin. 

AVhether  largely  from  the  loss  of  blood  from  the  kidneys  or 
from  other  causes,  the  red  cells  are  often  much  diminished,  but 
the  haemoglobin  suffers  still  more.  Laache  reports  an  average 
loss  of  nineteen  per  cent  of  the  red  cells  and  twenty-six  per  cent 
of  their  coloring  matter. 

Hayem  found  no  considerable  loss  of  red  cells  unless  the 
urine  was  hemorrhagic.  The  following  cases  illustrate  his  re- 
sults. 

CASE  I. — Acute  nephritis,  ending  in  recovery. 

Red  cells. 

March  17th,  1882 3,069,000 

March  31st,  1882 2,759,000 

April  7th,  1882 2,821,000 

May  1st,  1882,  alburainuria  ceased. 

May  17th,  1882 3,038,000 

May  31st,  1882 , 3,689,000 

CASE  II. — Acute  (puerperal)  nephritis;  recovery. 

Red  cells. 

April    6th,  1881 2,945,000 

9th,  1881 2,976,000 

"     12th,  1881,  no  albumin  in  urine. 

"     13th,  1881 3,137,500 

"     20th,  1881 3,310,000 

CASE  III. — Nephritis  (chronic  ?)  with  haematuria. 
Red  cells 2,821,000. 

(It  should  be  noted  that  Hay  em's  counts  are  low  on  the  aver- 
age, and  the  instrument  used  by  him  not  very  reliable.) 

Grawitz  in  acute  nephritis  records  3,400,000  red  cells  at  the 
beginning  of  the  third  week,  and  3,100,000  ten  days  later. 

Koblank1  counted  5,168,700  in  a  case  of  acute  nephritis  with 
oedema. 

1  Inaug.  Dissert.,  Berlin,  1889. 


ACUTE  NEPHRITIS. 


301 


Sadler  (loc.  cit.)  in  six  cases  of  acute  nephritis  found  in  two 
cases  3,590,000  and  2,262,000  red  cells;  in  the  other  four  practi- 
cally normal  counts. 

TABLE  XXXIV.— ACUTE  NEPHRITIS. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

56 

F 

22  200 

Temperature  102.5°. 

11 
45 
3 
23 
94 

F. 
M. 
F. 
M. 
F. 

4,068,000 
3,532,000 

14,000 
11,900 
12,200 
14,000 
13,200 
12,000 
11,700 
11,100 

'52' 
43 

50 

85 

Sixth  day. 
Ninth  day,  temperature  falling. 
Nineteenth  day. 

33 
22 
?,3 

M. 
M. 
M. 

3,904,000 
4,300,000 

9,300 
8,300 
7,600 

50 
48 
60 

Purpura  also. 

44 

F 

7,500 

65 

37 
20 
22 

M. 
M. 
F. 

5',  660!  666 

4,944,000 

6,800 
6,000 
5,400 
5,100 

78 
58 

Acute  parenchymatous. 
Acute  parenchymatous. 

In  none  of  the  few  cases  examined  at  the  Massachusetts 
Hospital  were  the  red  cells  much  diminished,  but  in  two  cases 
the  haemoglobin  was  very  low,  the  color  index  being  .62  in  one 
and  .61  in  the  other. 

The  blood  plates  are  much  increased  (Hayem)  and  fibrin 
slightly  increased. 

2.    White  Cells. 

Leucocytosis  is  usually  stated  to  be  the  rule,  lasting  often 
for  weeks  at  a  time  and  gradually  diminishing  in  convalescence. 

Hayem  gives  counts  of  14,973,  12,400,  15,000,  and  13,000. 

Koblank  (loc.  cit.)  and  Grawitz  each  in  a  single  case  found 
normal  counts  (7,300  and  5,600). 

Sadler  found  an  increase  in  only  one  of  his  six  cases,  and 
then  the  highest  point  reached  was  13,312. 

Of  the  thirteen  cases  of  Table  XXXIV.  leucocytosis  was 
present  in  six,  in  one  of  which  it  was  followed  for  three  weeks 
and  still  persisted,  but  it  is  my  own  belief  that  the  leucocytosi& 
of  acute  nephritis  is  due  either  to  loss  of  blood  by  the  kidney 


302  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

or  to  uraemia.     Where  these  conditions  are  absent  I  have  not 
found  any  leucocytosis. 

CHRONIC  DIFFUSE  AND   CHRONIC  PARENCHYMATOUS 
NEPHRITIS. 

Red  Cells. 

In  advanced  stages  the  counts  may  run  very  low,  but  more 
often  it  is  chiefly  the  haemoglobin  that  suffers  through  the  drain 
of  albuminoids  from  the  blood  into  the  urine. 
Hay  em  gives  the  following  figures : 
CASE  I. — Chronic  parenchymatous  nephritis. 

Red  cells.    Per  cent  haemoglobin. 

June  20th 4,309,000  43 

July  4th 4,216,000  44 

October  18th 2,945,000  34 

CASE  II. — Same  diagnosis. 

Red  cells.    Per  cent  haemoglobin. 

March    6th  . . . 2,619,500  36 

8th  .  -. 2,836,500  36 

23d 2,464,500  27 

^ 

Koblank  (loc.  tit.)  in  the  same  disease  found  3,291,700  red 
cells  in  a  single  case  with  much  oedema. 

Keinert  found  4,050,000  with  50  per  cent  of  haemoglobin  and 
3,604,000  with  62  per  cent  hemoglobin. 

Sadler: 

Red  cells. 
Case  1 4,120,000 

(  2,405,000— November  19th. 
"     2 j  1,100,000— January  14th. 

(  1,500,000— January  17th. 

"     3 4,300,000 

"     4 4,300,000 

i  3,737,500— June  28th. 
"     5 •]  3,593,700— July  3d. 

(  2,187,500— August  15th. 

,3,200,000— July    7th. 
u     6 •!  3,257,000— July  22d. 

(  3,137,000— August  21st. 


CHRONIC   PARENCHYMATOUS   NEPHRITIS. 


303 


Grawitz  in  an  acute  exacerbation  of  a  chronic  parenchyma- 
tous  nephritis  found  1,928,000  red  cells. 

The  Massachusetts  Hospital  cases  show  a  considerable 
anaemia  in  nine  out  of  the  thirty -five,  or  one-quarter  of  the  series. 
Great  concentration  is  probably  the  cause  of  the  very  high 
counts  in  certain  cases.  The  majority  of  cases  are  not  far  from 
normal  so  far  as  the  number  of  red  cells  goes,  and  the  haemo- 
globin is  also  very  little  diminished. 


CHRONIC  NEPHRITIS. 

Red  cells. 
Between  1,000,000  and  2,000,000  . . . 


Cases. 
1 


2,000,000 
3,000,000 
4,000,000 
5,000,000 
6,000,000 


3,000,000 2 

4,000,000 11 

5,000,000 12 

6,000,000 6 

7,000,000 3 


Color  index  averages  about  .' 


35 


White  Cells. 

Hayem  records  25,000,  19,000,  13,000,  10,000,  and  6,000  and 
concludes  that  the  counts  vary  much  not  only  in  different  cases 
but  in  the  same  case  at  short  intervals. 

Koblank  found  14,700  in  a  single  case. 

Sadler  in  one  case  found  6,300  in  November  and  16,000  in 
the  following  January;  12,000  in  another  case;  8,800,  7,700, 
and  1,916  in  others. 

TABLE  XXXV.,  A.— LEUCOCYTES  IN  CHRONIC  NEPHRITIS  WITH  UREMIA. 


Age. 

Sex. 

White 
cells. 

Remarks. 

Age. 

Sex. 

White 
cells. 

Remarks. 

32 

F. 

44,000 

Eclampsia. 

23 

M. 

12,500 

29 

F. 

22,  600 

58 

M. 

12,400 

29 

M. 

18,650 

Polynuclear  cells, 

50 

F. 

12,300 

83  per  cent. 

59 

M. 

12,100 

49 

F. 

16,800 

44 

M. 

11,300 

20 

F. 

15,800 

Differential  count 

31 

M. 

11,200 

normal. 

45 

F. 

6,600 

38 

M. 

15,000 

34 

F. 

4,600 

45 

M. 

15,000 

30 

M. 

4,200 

37 

M. 

14,200 

15 

F. 

13,800 

19  cases  average  14,495. 

25 

M. 

13,400 

304 


SPECIAL   PATHOLOGY    OF   THE   BLOOD. 


TABLE  XXXV.,  B.— CHRONIC  DIFFUSE  AND  CHRONIC  PARENCHYMATOUS 
NEPHRITIS.    No  UREMIA. 


Age. 

Sex. 

White  cells. 

Age. 

Sex. 

White  cells. 

Age. 

Sex. 

White  cells. 

41 

M. 

3,000 

50 

F. 

7,300 

43 

F. 

10,300 

30 

M. 

4,500 

34 

M. 

7,400 

56 

M. 

10,700 

58 

M. 

4,800 

55 

M. 

7.400 

47 

F. 

10,800 

30 

M. 

5,000 

17 

M,. 

7,500 

10 

F. 

11,000 

27 

M. 

5,100 

25 

M. 

7,600 

25 

M. 

11,200 

30 

F. 

5,200 

28 

M. 

7,600 

16 

F. 

12,700 

41 

M. 

5,500 

15 

F. 

7.700 

11 

M. 

13,000 

20 

F. 

6,250 

14 

M. 

7,750 

27 

M. 

13,000 

7 

M. 

6,400 

33 

M. 

7,900 

66 

M. 

14,000 

39 

M. 

6,500 

27 

F. 

8,300 

56 

F. 

14,000 

8 

M. 

6,500 

30 

M: 

8,300 

43 

M. 

14,500 

8 

M. 

6,800 

24 

F. 

9,000 

45 

M. 

16,300 

41 

M. 

6,800 

52 

F. 

9,800 

28 

M. 

7,000 

20 

F. 

10,000 

40  cases  average  8,  657. 

The  same  wide  range  i&  seen  in  Tables  XXXV.,  A  and  B, 
in  which  I  have  divided  the  ursemic  and  the  non-uraemic  cases 
into  separate  tables.  It  will  be  seen  from  these  that  fourteen  out 
of  nineteen  uraemic  cases  showed  leucocytosis,  while  thirty-one 
out  of  forty  non-uraemic  cases  showed  no  leucocytosis.  It  is 
difficult  to  suppose  that  this  is  mere  coincidence. 


CHRONIC  INTERSTITIAL  NEPHRITIS. 

Hayem  found  the  fibrin  more  increased  in  this  form  of  ne- 
phritis than  in  any  other,  and  the  anaemia  less  pronounced. 
Grawitz  distinguishes  two  stages : 

I.  As  long  as  the  heart  is  strong  enough  to  overcome  the  in- 
creased resistance  at  the  pejiphery  and  the  disturbances  of  cir- 
culation are  not  marked,  the  blood  is  normal. 

II.  When  compensatory  hypertrophy  is  no  longer  sufficient 
to  do  the  work  of  forcing  the  blood  through  the  system,  the 
usual  effects  of  failing  compensation  (see  Heart  Disease,  page 
296)    appear    (dilution    and   subsequent  concentration  of  the 
blood). 

The  white  cells  are  normal. 


CHRONIC   INTERSTITIAL   NEPHRITIS. 


305 


TABLE  XXXVI.,  A.— CHRONIC  INTERSTITIAL  NEPHRITIS. 


Age. 

g 

02 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

39 
Adult. 
46 

M. 
F. 
M. 

M. 

6,040,000 
4,548,000 
4,244,000 

19,381 
15,000 
12,000 

9,724 

80 
50 
67 

Ursemiccoma;  moribund. 
Ursemic  ;  mitral  stenosis. 
Three  and  one-half  hours  after  a 
meal. 
Ursemic  ;  moribund 

20 

34 
69 

M. 

F. 

M 

4,088,000 
3,536,000 

6,000 

8,300 
8  500 

66 
52 

57 
87 

March  23d. 
"      30th. 

32 

M 

6,000 

65 

TABLE  XXXVI.,  B.  —  PYELONEPHRITIS. 


6 
^ 

Age. 

$ 

02 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 
2 

24 
26 

F. 
F 

3,056,000 
2,976,000 
2,696,000 
3,272,000 
4,  200,  000 

21,200 
15,200 
18,800 
25,200 
16,  800 

41 
38 
33 
33 

March  10th.     Uraemia. 
"      13th. 
"      27th. 
April  14th. 
Perinephritic  abscess  too 

3 

4 

33 
26 

M. 
F. 

4,536,000 
2,356,000 

15,550 

7,280 

36 
65 

Cystitis  also. 

TABLE  XXXVI.,  C. -CYSTIC  KIDNEY. 


Age. 

X 

£ 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

55 

M 

3  664,000 

6,400 

Adult  cells,    72  per   cent.     Sup- 

posed cancer.     Enormous  firm 
tumor  on  each  side.     Autopsy. 

The  cases  recorded  in  Table  XXXVI.,  A,  are  probably  not 
inconsistent  with  these  rules.  Of  the  four  cases  with  leuco- 
cytosis  three  were  ursemic,  and  in  the  fourth  the  influence  of 
digestion  is  seen.  The  haemoglobin  is  lower  than  we  should 
expect  from  Grawitz's  account. 

Urcemia,  it  would  appear  from  these  tables,  may  cause  leu- 
cocytosis  or  at  any  rate  is  not  infrequently  associated  with  it. 
Aside  from  uraemia  and  hemorrhage,  nephritis  probably  does 
not  cause  leucocytosis. 
20 


306 


SPECIAL   PATHOLOGY   OF   THE    BLOOD. 
PYELO-NEPHRITIS. 


Table  XXX VI.,  B,  speaks  for  itself.     The  ancemia  is  often 
severe  and  leucocytosis  is  the  rule. 


STONE  IN  THE  KIDNEY. 


(See  Table  XXXVII.,  A.)  The  state  of  the  blood  depends 
on  the  amount  of  ulceration  caused  by  the  stone ;  when  this  is 
considerable  we  have  leucocytosis. 


TABLE  XXXVII.,  A.— STONE  IN  THE  KIDNEY. 


No. 

Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

\ 

1 

22  800 

85 

Tender  in  loin 

B 

19 

IVT 

16,200 
15,200 

Much  pus  in  urine 

3 
4 
5 

25 

48 

M. 
F. 
IVf 

4,350,000 
4,160,000 

14,750 
9,000 
8  990 

78 
65 

6 

7 

8 
9 

58 

52 

45 

M. 

M. 
M 

5,680,000 
4,340,000 
6,100,000 
3,048,000 

8.000 
8,000 
16,500 
7,500 
7,500 

30 
95 

Much  pus  in  urine. 
Two  weeks  later. 

10 

51 

M 

6  000 

95 

Uric  acid,  stone  passed 

11 

30 

M. 



4,980 

85 

TABLE  XXXVII.,  B.— FLOATING  KIDNEY. 


No. 

Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 
2 
3 
4 
5 

37 
41 
23 
43 

38 

F. 
F. 
F. 
F. 

F 

5,056,000 
4,684,000 
5,400,000 
4,700,000 

9,200 
9,000 
6,000 
2,400 

75 
75 
69 
76 
75 

Aneurism  of  arch  also. 

6 

94 

F 

80 

5 
6 

38 
24 

F. 
F. 

4,416,000 

5,800 

7,  600 

67 

80 

A  large  number  of  similar  counts  might  be  quoted. 
Diagnostic  Value. 

Cancer  would  also  cause  leucocytosis,  but  would  not  increase 
fibrin  as  a  rule,  while  most  cases  of  stone  with  ulceration  do 
increase  fibrin. 


ACUTE  BRONCHITIS.  307 

FLOATING  KIDNEY. 

The  blood  is  normal.  This  fact  has  some  diagnostic  value ; 
for  example,  when  we  confound  appendicitis  with  floating  kid- 
ney, as  has  been  done  (see  page  230) .  The  presence  of  leucocy- 
tosis  excludes  the  latter  and  favors  the  former.  Most  tumors 
or  abscesses  with  which  a  floating  kidney  might  be  confused 
could  be  distinguished  by  the  same  criterion. 

PYO-NEPHROSIS. 

CASE  I. — Female,  36;  leucocytes,  16,200,  of  which  85  per 
cent  are  neutrophiles.  Half  a  pint  of  pus  found  at  operation. 

CASE  II.— July  25th— red  cells,  3,856,000;  white  cells,  9,800; 
haemoglobin,  45  per  cent.  July  29th— Bed  cells,  3,450,000; 
white  cells,  9,000;  haemoglobin,  55  per  cent.  August  3d— 
White  cells,  6,650.  August  6th— Operation.  Pint  of  foul  pus. 
Death. 

DISEASES    OF    THE    LUNGS. 
BRONCHITIS. 

"  Acute  catarrhal  and  chronic  purulent  bronchitis  have  rela- 
tively little  leucocytosis  in  most  cases"  (v.  Limbeck). 

Except  for  this  and  a  few  other  passing  references,  there  is 
hardly  anything  in  literature  on  the  blood  in  bronchitis,  so  that 
I  shall  be  forced  to  base  my  statements  chiefly  on  the  few  counts 
recorded  at  the  Massachusetts  General  Hospital. 

1.  ACUTE  BRONCHITIS. 

Aside  from  "  capillary  bronchitis,"  cases  are  not  infrequently 
seen  in  which  the  signs  are  simply  those  of  general  bronchitis 
of  the  finer  tubes,  yet  the  symptoms  are  much  more  like  pneu- 
monia. Whatever  may  be  the  real  conditions  in  the  lungs  of 
such  patients,  their  blood  is  not  infrequently  exactly  like  that 
of  pneumonia  and  does  not  help  at  all  in  the  differential 
diagnosis  between  the  two  diseases  (see  Cases  1  and  2,  Table 
XXXYIIL,  A). 


308 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


TABLE  XXXVIII.,  A. — ACUTE  BRONCHITIS. 


Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

Remarks. 

70 
56 

9,9, 

F. 
M. 
M. 

4,420,000 
4,800,000 

41,000 
26,000 
23  450 

70 
65 
67 

Temperature,  103°. 
Temperature    101° 

41 
26 

F. 
M. 

4,192,000 

15,000 
11,300 
17,  600 
14,200 

65 
70 

November  5th. 
November  16th. 
November  25th. 
Temperature   101  5° 

28 
46 

F. 
M. 

6,196,000 

12,000 
11,800 

65 

Temperature,  104° 

9,0 

M. 

10  600 

65 

Temperature    104° 

40 

M. 

10  300 

Temperature    101° 

49, 

M. 

9  300 

50 
50 
52 

F. 
M. 
M. 

5,260,000 
5,952,000 

8,000 
7,900 
7,000 

72 
50 
70 

25 

M. 

7,000 

74 

Temperature,  103°. 

59 

F. 

6,800 

36 
29 

M. 
M. 

4,392,000 

6,000 
8.600 
4,000 

72 
80 

October  31st. 
November  3d. 
Temperature,  102°. 

TABLE  XXXVIII.,  B.— CHRONIC  BRONCHITIS. 


Age. 

1 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

Adult. 

48 

27 

61 
20 

M. 
M. 

F. 

M. 
F 

3,680,000 

5,384,000 
4,300,000 

18,500 
15,000 

8,800 

8,000 
7,  925 

63 

73 

63 

78 

Chronic  febrile,   with  laryngitis. 
.  Recovery. 
Constipation  ;  neurasthenia  ;  two 
weeks  afebrile. 
Five  months. 

18 

26 
29 

20 

M. 

F. 
F. 
M. 

4,700,000 
4,100,000 

7,792 

6,700 
5,500 
5,062 

70 
61 

Keratitis,     conjunctivitis.        No 
symptoms. 
Asthma. 
Empyema  of  the  antrum. 
One  month. 

In  the  majority  of  acute  cases,  however,  the  blood  shows  no 
changes  unless  concentration  due  to  cyanosis  be  present  (see 
Cases  4  and  7,  Table  XXXVIII.,  A). 

In  chronic  cases  (Table  XXXVIII. ,  B)  leucocytosis  is 
very  uncommon,  more  so,  I  think,  than  the  table  represents. 
If  more  counts  were  added,  nearly  all,  I  think,  would  bo 
normal. 


EMPHYSEMA   AND   ASTHMA. 


309 


The  red  cells  and  hemoglobin  show  no  changes  to  speak  of 
in  either  acute  or  chronic  cases. 

The  blood  has  no  diagnostic  value  so  far  as  I  know  except 
that  when  pneumonia  is  in  question  a  normal  count  of  white 
cells  speaks  against  it  and  in  favor  of  bronchitis.  If  emphy- 
sema is  also  present  it  sometimes  produces  a  different  blood 
condition  from  that  of  simple  bronchitis. 


EMPHYSEMA  AND  ASTHMA. 

Grawitz  reports  an  increase  in  the  number  of  red  cells  in 
emphysema,  which  he  believes  to  be  due  to  cyanosis  and  to  cover 
up  the  really  anaemic  condition  of  the  blood  of  many  patients. 
Practically  the  same  conditions  are  present  as  in  the  cyanosis  of 
heart  disease  (see  page  296)  and  the  concentration  of  the  blood 
is  brought  about  in  the  same  way.  Leichtenstern 1  noticed  a  di- 
minution in  haemoglobin  at  the  time  when  the  heart  first  fails, 
due  probably  to  the  diminished  blood  pressure  which  allows  the 
lymph  from  neighboring  tissues  to  flow  into  the  vessels  and 
dilute  the  blood. 

In  both  asthma  and  emphysema  it  has  been  noted  by 
Miiller,2  Gollasch,3  Gabritschewsky  4  and  others  that  eosinophiles 
are  very  numerous  in  the  sputum,  and  Fink 2  also  noted  an  in- 
crease of  the  same  cells  in  the  blood,  running  as  high  as  14.6 
per  cent  instead  of  the  normal  one  to  two  per  cent.  This  increase 
is  present  only  at  the  time  of  the  paroxysm  and  for  a  short  time 
before  and  after  it.  Billings  5  reports  the  following  counts : 


January  26th. 

February  4th. 

February  llth. 

Bed  cells  

3  911  000 

4  221  000 

4  630  000 

White  cells  

8  300 

7  500 

7  600 

Haemoglobin 

68     per  cent 

75  per  cent 

Poly  morp  honuclear 
cells  

36          " 

Lymphocytes  (small)  .  . 
Lymphocytes  (large)  .  . 
Eosinophiles.  .  . 

5 
5.2 

53  6  1     " 

38  2  per  cent 

33  9  per  cent 

Few  normoblasts 

No  nucleated 

red  cells. 

"  Ueber  das  Hb-Gehalt  des  Blutes, "  etc. ,  Leipzig,  1878. 
2Ref.  in  Fink,  "Beitrage  z.  Kennt.  des  Eiters,"  Dissert.,  Bonn,  1890. 
3Fortschritt£der  Med.,  1889. 
4  Arch.  f.  exp.  Path,  und  Pharm.,  1890,  p.  83. 
6  New  York  Med.  Journal,  May  22d,  1897. 


310 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


Tlieir  presence  in  increased  numbers  before  a  paroxysm  makes 
it  possible  to  predict  its  coming  (v.  Noorden,  Schwerskewski). 
As  this  applies  only  to  pure  bronchial  asthma  and  not  to  cases 
secondary  to  disease  of  the  heart  or  kidney,  Schreiber  states 
that  we  are  enabled  to  distinguish  bronchial  from  cardiac  or  renal 
asthma  by  the  increase  of  eosinophiles  in  the  blood  and  sputa 
in  bronchial  cases,  which  does  not  occur  in  asthma  due  to  cardiac 
and  renal  trouble. 

ASTHMA. 


Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
hffimo- 
globin. 

Remarks. 

26 

M 

32,500 

Fifth.      Temperature  100°.      Bron- 

50 

F 

19,200 
19  800 

50 

chitis  and  emphysema. 
Seventh.     Temperature  normal. 
Typical   bronchial  asthma    during 

70 
29 

M. 
M 

5,500,000 

13,000 
9,750 

paroxysm." 
Chronic  asthma  and  emphysema  in 
paroxysm  ;    polynuclear  cells,  79 
per  cent. 

For  Pneumonia,  see  page  184. 

For  Phthisis,  see  page  255. 

For  Abscess  of  Lung,  see  page  235. 

SYPHILIS  OF  THE  LUNG. 

In  a  case  of  syphilitic  infiltration  of  the  lung  (autopsy — Drs. 
Councilman  and  Wright)  recently  observed  at  the  Massachusetts 
Hospital  the  leucocytes  rose  rapidly  from.  8,700  to  27,400  as 
death  approached. 


PART  V . 


DISEASES    OF    THE    NERVOUS    SYSTEM,    CON- 
STITUTIONAL   DISEASES,    AND    HEMOR- 
RHAGIC  DISEASES. 


CHAPTEE  YHI. 

DISEASES    OF    THE    NERVOUS    SYSTEM. 
NEURITIS. 

IN  a  single  case  of  multiple  neuritis,  febrile  and  apparently 
of  an  infectious  nature,  the  following  counts  are  found  in  the  rec- 
ords of  the  Massachusetts  General  Hospital : 


Date. 

Temperature. 

Red  cells. 

White 
cells. 

Per  cent 
haemoglobin. 

July  10th 

101°.                 

4,816,000 

25,000 

42 

"      1  3th 

24,800 

"     16th 

18,  700 

"     20th   .. 

21,000 

"     25th  

4,320  000 

16,000 

60 

"     31st 

(No  fever  )  .         ... 

28,  700 

AuEjust  7th 

u             u 

19,500 

"       20th 

u            « 



23,200 

The  patient,  a  boy  of  eleven,  recovered  and  left  the  hospital 
well. 

But  these  changes  occur  also  in  alcoholic  (afebrile)  neuritis, 
as  the  following  counts  show. 


Case. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

1 

3  608  000 

15,  000 

75 

2  

3,260,000 

14,000 

64 

3                                             .    ..  . 

13,  700 

60 

4 

11,200 

68 

5 

7,700 

80 

6 

6,700 

82 

312 


SPECIAL   PATHOLOGY   OF   THE    BLOOD. 


In  all  cases  the  counts  were  made  just  at  mealtime,  so  that 
the  leucocytosis  is  not  due  to  digestion.  Gastritis  was  not 
present  in  either  case. 

One  case  of  post-diphtheritic  neuritis  in  a  child  of  eight 
showed  the  presence  of  anaemia  only:  Eed  cells,  3,850,000; 
white  cells,  7, 393 ;  haemoglobin,  70  per  cent. 

Neuritis  in  lead  poisoning  does  not  affect  the  count  of  leuco- 
cytes, as  twenty -five  cases  studied  at  the  Massachusetts  Hospital 
have  shown. 

Neuralgia,  whether  facial,  intercostal,  sciatic,  or  ovarian, 
showed  normal  blood  in  numerous  cases  examined  at  the  Massa- 
chusetts Hospital. 

DISEASES     OF    THE    BRAIN. 

Meningitis  (see  Inflammation  of  Serous  Membranes,  page  248). 

Zappert  in  one  case  of  brain  abscess  found  only  4,000  white 
cells. 

In  pachy  meningitis  hcemorrJwgica  and  cerebral  syphilis  (one 
case  of  each)  v.  Jaksch  found  leucocy  tosis.  My  own  experience 
has  been  the  same. 

Cerebral  and  cerebellar  tumors  have  no  effect  on  the  blood  as 
far  as  could  be  judged  from  nine  counts  in  the  former  and  three 
in  the  latter  disease.  Von  Jaksch  found  slight  leucocytosis  in 
two  cases  of  brain  tumor  and  one  of  cysticercosis.  Zappert  found 
normal  blood  in  one  case  of  cerebral  tumor. 

Fresh  cerebral  hemorrhage  usually  causes  leucocytosis,  as  the 
following  table  shows : 


Age. 

(Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

42 
53 

47 

M. 
M. 

M 

5,  51  2,0(30 

31,000 
30,000 
25,000 
19  400 

95 
'85* 

Autopsy. 
Polynuclear  cells,  92  per  cent. 
Autopsy. 
Autopsy 

70 

F 

16  800 

68 

Hemorrhage  four  days  before  count 

87 

M 

5,560,000 

15,600 
12  300 

90 
70 

Autopsy. 

38 

M 

10  400 

58 

Conscious  ;  recovered. 

87 

M 

10  300 

90 

Autopsy 

<65 

M 

10  200 

60 

GENERAL    PARALYSIS   OF   THE    INSANE.  313 

CHOREA   AND  TETANY. 

Chorea  showed  in  twelve  cases  normal  blood  except  for  in- 
creased percentages  of  eosinophiles,  as  in  Zappert's  two  cases, 
which  Louga  confirms. 

Burr  has  made  a  careful  study  of  the  blood  in  thirty-six 
cases  and  arrived  at  the  following  conclusions :  There  is  usually 
a  slight  diminution  in  red  cells  and  a  moderate  diminution  in 
haemoglobin.  Any  severe  grade  of  anaemia  is  due  to  some  com- 
plication. He  did  not  record  the  leucocytes.  Tetany  shows  no 
blood  changes. 

DISEASES    OF    THE     SPINAL    CORD. 

Chronic  diseases  of  the  spinal  cord,  such  as  tabes  dorsalis, 
syringomyelia,  spastic  paraplegia,  diffuse  myelitis,  paralysis 
agitans,  and  progressive  muscular  atrophy,  are  found  to  pro- 
duce no  changes  in  the  blood. 

For  Spinal  Meningitis,  see  page  249. 

GENERAL  PARALYSIS   OF  THE  INSANE. 

Capps '  has  made  a  careful  study  of  the  blood  in  nineteen 
cases  and  comes  to  the  following  conclusions : 

1.  Eed  corpuscles  and  haemoglobin  are  always  slightly  dim- 
inished, the  averages  being  4,789,900  and  85  per  cent. 

2.  Most  cases  show  a  slight  leucocytosis — 22  per  cent  above 
the  normal  on  the  average.     Early  cases  may  have  no  leucocy- 
tosis. 

3.  The  differential  counts  show  that  the  blood  is  slightly 
older  than  that  of  normal  adults.     The  polymorphonuclear  leu- 
cocytes average  nearly  74  per  cent  and  the  smaller  forms  of  lym- 
phocytes only  14.2  per  cent,  while  the  larger  forms  of  lympho- 
cytes are  relatively  numerous,  averaging  7.8  per  cent.     In  a  few 
cases  the  eosinophiles  were  very  numerous2  (8.7  and  6.4  per  cent) . 

4.  At  the  time  of  convulsions  the  red  cells  and  haemoglobin 
are  apparently  increased  (due  no  doubt  to  the  violent  muscular 

1  American  Journal  of  the  Medical  Sciences,  July,  1896. 

2Roncoroni  (Archiv.  di  Psichiat.  Scien.  1894,  p.  293)  finds  eosiDO- 
philes  increased  even  to  twenty -five  per  cent  in  the  agitated  and  violent 
cases. 


314  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

contractions    which   raise  blood  pressure  and  concentrate  the 
blood,  or  to  cyanosis). 

There  is  a  sudden  and  pronounced  increase  in  the  leucocytes 
during  and  after  convulsions  or  apoplectiform  attacks.  That 
this  is  not  due  to  concentration  of  the  blood  or  to  stasis  Capps 
thinks  is  shown  by  the  fact  that  not  only  the  number  but  the 
differential  count  of  white  cells  show  changes,  the  "  large  mono- 
nuclear"  cells  being  relatively  increased,  sometimes  as  high  as  25 
per  cent.  Myelocytes  were  seen  in  one  case  after  the  convulsions, 
and  especially  just  before  death  when  in  a  leucocytosis  of  18,250 
11  per  cent  were  myelocytes.1 


HYSTERIA  AND  NEURASTHENIA;    HYPOCHONDRIASIS. 

A  large  number  of  cases  have  been  counted  at  the  Massa- 
chusetts General  Hospital,  with  a  view  to  excluding  other 
diseases.  The  blood  count  is  always  normal  except  that  in  a 
certain  number  of  the  hysterical  cases  eosinophiles  are  rela- 
tively increased,  and  that  many  of  the  neurasthenics  show  the 
increased  percentage  of  lymphocytes  which  I  have  alluded 
to  above  (page  97)  as  characteristic  of  a  variety  of  debilitated 
conditions. 

Marked  ancemia  is  seldom  present,  although  the  haemoglobin 
is  not  infrequently  as  low  as  65  per  cent.  Beinert 2  found  the 
haemoglobin  under  60  per  cent  in  only  4  out  of  48  cases  of  hys- 
teria, and  in  none  of  36  neurasthenics. 

The  value  of  the  blood  examination  in  such  cases,  like  that  of 
the  urine  or  the  lungs  in  hysteria,  is  as  negative  evidence,  and  in 
this  respect  it  is  important.  When  the  discrepancy  between 
complaints  and  signs  is  great,  we  want  to  be  doubly  sure  that 
nothing  hidden  escapes  our  notice,  and  the  blood  examination  is 
one  of  the  most  valuable  adjuvants  we  have  in  the  discovery  of 
deep-seated  inflammation  or  malignant  disease,  as  well  as  in 
giving  us  a  general  measure  of  the  patient's  degree  of  bodily 
health  as  distinguished  from  nervous  force.  The  former  may 
be  high  when  the  latter  is  low,  or  both  may  be  low,  and  the  dis-» 

1  Leucocytosis  has  been  repeatedly  noticed  in  convulsions  from  various 
causes.     Probably  the  irritant  which  causes  the  motor  discharge  also  acts 
on  the  leucocytes  by  chemotaxis. 

2  Munch,  med.  Woch.,  1805,  No.  14. 


CONSTITUTIONAL   DISEASES.  315 

tinction  marks  out  two  classes  of  cases  in  which  somewhat  dif- 
ferent treatment  is  appropriate.  There  is  no  use  in  undertak- 
ing to  make  "  blood  and  fat"  when  the  patient  has  already  plenty 
of  each,  though  it  may  be  well  to  carry  out  the  same  regime  as  a 
matter  of  suggestion. 

MENTAL    DISEASES. 

The  association  of  anaemia  with  insanity  is  too  frequent  to  be 
a  mere  coincidence,  though  it  is  hard  to  make  either  serve  as  a 
cause  for  the  other.  Very  possibly  they  should  both  be  looked 
upon  as  symptoms  of  a  common  underlying  (unknown)  cause. 

This  form  of  anaemia  has  been  noticed  by  Houston1  in  mel- 
ancholia and  general  paralysis,  and  by  Smith2  in  various  forms  of 
insanity.  - 

Krypiakiewicz8  noticed  an  increase  of  eosinophiles  in  acute 
forms  of  insanity  but  not  in  the  chronic  forms.  The  leucocyto- 
sis  of  acute  delirium*  is  exemplified  by  the  following  case  from 
the  Massachusetts  Hospital  records : 

A  girl  of  fifteen;  acute  delirium;  leucocytes,  12,750;  no  food 
for  eight  hours;  red  cells,  4,510,000;  haemoglobin,  63  per  cent: 

Puerperal  mania  is  to  be  distinguished  from  the  delirium  of 
puerperal  sepsis  by  the  fact  that  the  latter  shows  leucocytosis 
with  increased  percentage  of  polymorphouuclear  cells,  while 
the  former  has  no  leucocytosis  (if  uncomplicated)  and  the 
eosinophiles  are  apt  to  be  increased  6  (diminished  in  sepsis). 

A  case  of  puerperal  mania  seen  by  the  writer  showed :  Bed 
cells,  5,210,000;  white  cells,  6,500;  haemoglobin,  84  per  cent; 
eosinophiles,  8  per  cent. 


CONSTITUTIONAL    DISEASES. 
OBESITY. 

Oertel  distinguishes  a   plethoric   and  an  anaemic   form  of 
obesity  not  merely  clinically  but  by  the  evidence  of  post-mortem 

1  Houston :  Boston  Med.  and  Surg.  Journal,  January  llth,  1894. 

1  Smith  :  Jour,  of  Ment.  Sc  ,  October,  1890. 

^Krypiakiewicz:  Wien.  med.Woch.,  1892,  No.  25. 

4  Ref .   in  Klein-Volkmann's  "Sammlung  klin.  Vortrage,"   December 
1893. 

Neusser  .  Loc.  cit. 


310  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

examinations.  He  believes  that  there  is  a  real  over-filling  of 
the  vessels  in  the  first.  The  second  form  occurs  most  often  in 
women. 

Kisch  examined  (with  v.  Fleischl's  instrument)  the  haemo- 
globin of  100  obese  patients;  79  showed  over  100  per  cent  of 
haemoglobin,  1  reaching  120  per  cent,  while  the  other  21  were 
anssniic. 

DIABETES. 

There  is  nothing  characteristic  about  the  blood  except  the 
increased  amount  of  sugar  to  be  detected  (.57  per  cent  as  against 
.1  normally);  but  this  is  not  a  clinically  applicable  test. 

Two  simple  tests  for  diabetic  blood  have  recently  attracted 
attention : 

1.  Bremer's  test:  Heat  thick-spread  blood  films  to  135°  C. ; 
cool  and  stain  with  one-per-cent  aqueous  solution  of  Congo  red  for 
two  minutes.     The  blood  if  diabetic  looks  yellow  (to  the  naked 
eye).     Normal  blood  similarly  treated  looks  red.     Staining  with 
methyl  blue  also  shows  a  difference  between  normal  blood  and 
diabetic   blood.      The   normal   is  blue,  the  diabetic  yellowish 
green. 

2.  Williamson's  test:  Make  a  mixture  of 

Blood,        .         .         .         .         ...         .  20  c. ram.  (2  drops). 

Aqueous  methyl  blue  (1 : 6, 000),  .  .  .  1  c.c. 
Liquor  potassse,  60  per  cent  (sp.  gr. ,  1.058),  .  40  c.c. 
Water, 40  c.  c. 

Xiet  the  mixture  stand  three  to  four  minutes  in  boiling  water. 
With  diabetic  blood  the  mixture  turns  yellow,  with  normal  blood 
it  does  not.  Williamson  has  found  this  test  positive  in  eleven 
diabetics  and  negative  in  one  hundred  cases  of  other  diseases. 
Bremer  claims  that  by  his  method  cases  of  diabetes  can  be 
recognized  before  sugar  appears  in  the  urine  or  after  it  has 
(temporarily)  disappeared.  Le  Goif  confirms  the  value  of  the 
test.  Eichner  and  Folkel  find  Bremer's  reaction  to  be  as  stated, 
but  find  similar  color  changes  in  leukaemia,  Hodgkiu's  disease, 
and  Graves'  disease,  and  changes  something  like  it  in  a  variety 
of  cachectic  conditions.  Badger  has  studied  the  blood  of  dia- 
betics, leukaemics,  cases  of  Graves'  disease,  and  other  cases  at 
the  Massachusetts  Hospital.  Only  in  Graves'  disease  did  he 
find  reactions  like  those  of  diabetic  blood. 


GOUT.  317 

The  alkalinity  has  been  said  to  be  greatly  diminished,  espe- 
cially in  the  fatal  coma,  but  v.  Noorden  thinks  the  tests  are 
unreliable. 

Fat  is  often  increased  in  the  blood,  up  to  about  twelve  times 
the  normal,  so  that  the  serum  is  milky,  and  glycogen  has  been 
demonstrated  microchemically  in  the  corpuscles. 

Red  Cells. 

Sugar  in  the  blood  draws  water  from  the  tissue  into  the 
vessels,  thereby  diluting  the  blood;  but  in  a  short  time  the  blood 
frees  itself  of  the  excess  of  sugar  and  fluid  through  increased 
diuresis  so  as  to  concentrate  the  blood. 

These  two  alternating  influences  serve  to  explain  the  widely 
different  counts  of  different  observers. 

Toward  the  end  of  the  disease  a  decided  cachexia  often  de- 
velops, the  anaemia  of  which  may  be  temporarily  covered  up  by 
the  concentration  above  noted,  or  accentuated  by  the  dilution 
which  sometimes  occurs.  Accordingly  we  may  find  the  corpus- 
cles increased,  normal,  or  diminished  in  different  cases  or  at 
different  times  with  the  same  case. 

Grawitz  counted  4,900,000  red  cells  in  a  patient  in  compara- 
tively good  health,  and  three  weeks  later,  when  the  patient  had 
just  been  seized  with  the  fatal  coma,  the  count  showed  6,400,000 
per  cubic  millimetre. 

The  white  cells  show  no  constant  changes,  except  that.v. 
Limbeck  has  noted  in  several  cases  that  the  digestion-leucocy- 
tosis  is  unusually  large  even  without  previous  fasting.  Von 
Jaksch  found  leucocytosis  in  one  of  his  eight  cases,  but  on  this 
point  as  on  many  others  his  results  are  almost  unique.  The 
only  similar  observation  is  that  of  Habershon,1  who  reports 
moderate  leucocyosis,  decreased  by  strict  diet.  In  thirteen 
cases  I  have  never  seen  leucocytosis.  A  single  case  of  diabetic 
coma  showed  4,200  leucocytes  per  cubic  millimetre. 

GOUT. 

A  few  cubic  centimetres  of  serum  from  gouty  blood  made  acid 
with  acetic  acid  (six  drops  of  a  twenty-eight-per-cent  solution 
to  every  drachm  of  serum)  deposit  crystals  of  uric  acid  on  a 

1  St.  Bartholomew  Hosp.  Rep. ,  1890,  p.  153. 


318  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

thread  in  from  eighteen  to  forty-eight  hours ;  but  this  is  not  al- 
ways to  be  found,  and  is  by  no  means  peculiar  to  gout. '  Uric 
acid  is  to  be  found  in  the  blood  in  pneumonia,  cirrhotic  liver, 
nephritis,  grave  anaemia,  leukaemia,  and  gravel;  also  in  health 
and  after  a  meal  of  calf's  thymus  or  any  food  containing  much 
nuclein. 

The  red  corpuscles  show  no  special  changes  except  in  severe 
chronic  cases  which  are  sometimes  anaemic.  The  white  cells  are 
increased  according  to  Neusser,  while  v.  Limbeck  and  Grawitz 
found  the  blood  wholly  normal. 

It  is  particularly  in  this  disease  that  Neusser  supposed  the 
"  perinuclear  basophilic  granulations"  to  exist  in  the  white  cells, 
which  he  believes  to  be  characteristic  of  any  "  uric-acid  diath- 
esis." Futcher  has  conclusively  disproved  this.  Fibrin  is  in- 
creased in  acute  cases. 

MYXCEDEMA. 

Le  Breton2  examined  the  blood  in  one  case  before  and  after 
thyroid  treatment  and  found  after  forty  days'  treatment  that  the 
red  cells  had  risen  from  1,750,000  to  2,450,000,  the  white  from 
4,500  to  9,600,  and  the  haemoglobin  from  65  to  68  per  cent. 

The  remarkably  high  color  index  in  this  case  before  treat- 
ment (nearly  2. !)  corresponds  with  the  observations  of  Le  Breton 
in  the  dried  specimen,  which  showed  a  decided  increase  in  the 
size  of  the  red  corpuscles.  He  also  noticed  before  instituting 
the  thyroid  treatment  the  presence  of  nucleated  red  cells  and 
an  excess  of  the  polymorphonuclear  form  of  leucocytes.  Under 
treatment  the  nucleated  red  cells  disappeared  and  the  lympho- 
cytes rose  to  their  normal  per  cent. 

Putnam  3  has  watched  a  similar  case  in  which  the  red  cells 
rose  from  3,120,000  to  5,700,000  under  thyroid  treatment. 

Murray  4  has  collected  23  cases  with  blood  examinations.  Of 
these  7  showed  normal  blood,  10  were  anaemic,  4  had  leucocyte- 
sis,  and  2  had  both  anaemia  and  leucocytosis. 

1  It  is  important  to  evaporate  the  serum  at  a  temperature  not  above  70° 
F. ,  otherwise  crystals  will  not  form. 

2  Le  Breton :  Ref.  in  Wien.  med.  Blatter,  1895,  p.  49. 

3  Putnam  :  Eef.  in  Murray's  article  in  "Twentieth  Century  Practice  of 
Medicine,"  vol.  iv. 

4 Murray :  "Twentieth  Century  Practice  of  Medicine,"  vol.  iv.,  p.  710. 


CRETINISM. 


319 


Kraepelin  :  noticed  (like  Le  Breton)  a  marked  increase  in  the 
average  diameter  of  the  corpuscles  in  three  cases,  even  when  the 
count  and  the  haemoglobin  were  normal. 

I  have  had  an  opportunity  to  examine  the  blood  in  three 
cases  of  this  disease,  but  did  not  find  anything  remarkable  in 
any  of  them. 


Case. 

Red  cells. 

White  cells. 

Per  cent 
Haemoglobin. 

1  . 

4,670,000 

6,000 

87 

2  

4,460,000 

8,800 

3 

4  856  000 

5  200 

80 

Differential  counts  were  made  in  three  cases  and  no  increase 
in  the  size  of  the  corpuscles,  such  as  Le  Breton  and  Kraepelin 
saw,  was  present  in  these  cases.  The  count  showed: 


Case. 

Polymorphonuclear 
cells. 

Lymphocytes. 

Eosinophiles. 

1  . 

67 

28 

5 

2  

67 

27.8 

4.4 

3 

74 

26 

The  increase  of  eosinophiles  in  two  of  these  cases  may  per- 
haps be  due  to  the  skin  troubles  present  in  the  disease. 

J.  J.  Thomas  found  a  few  myelocytes  in  a  case  of  Putnam's. 

CRETINISM. 

Koplik2  records  the  following  in  two  cases  of  sporadic 
cretinism : 

CASE  I. — Fifteen  months  old;  advanced  stage  of  disease. 
Hemoglobin,  18  per  cent. 

CASE  II.— Eed  cells,  3,026,000;  white  cells,  13,500;  hemo- 
globin, 105  per  cent.  This  high  haemoglobin  corresponds  to 
normal  foetal  blood.  The  child  was  nine  weeks  old,  but  its  back- 
ward development  is  mirrored  in  the  blood.  As  the  case  im- 
proved under  thyroids  the  haemoglobin  came  down. 


'Kraepelin  :  Deut.  Arch.  f.  klin.  Med.,  vol.  xlix.,  p.  587. 
2  New  York  Medical  Record,  October  2d,  1897. 


320  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


GRAVES'  DISEASE    (BASEDOW'S  DISEASE;  EXOPHTHALMIC 

GOITRE). 

The  blood  is  normal,  except  for  an  occasional  associated 
chlorosis  and  sometimes  a  marked  lymphocytosis.  In  one  case 
I  found  51.3  per  cent  of  lymphocytes  and  1  per  cent  of  mye- 
locytes  in  1,000  leucocytes,  the  polymorphonuclear  cells  being 
only  48  per  cent ;  but  in  fourteen  other  cases  I  have  never  found 
this  again.  The  same  fact  has  been  noticed  by  Neusser  (cited 
in  Klein,  loc.  cit.}. 

Oppenheimer1  found  the  red  cells  and  haemoglobin  normal  in 
two  cases.  Yon  Jaksch2  in  one  case  "  complicated  with  myx- 
oedema"  found  3,818,000  red  and  8,000  white  cells. 

The  association  of  Graves'  disease  with  chlorosis  is  illus- 
trated by  two  cases  from  Zappert  :3 


Case. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

1 

2,858,000 

3,800 

32 

2                         

2,738,000 

3,800 

30 

The  same  writer  found  eosinophiles  much  increased  (8.5  per 
cent)  in  one  out  of  four  cases. 

ADDISON'S    DISEASE. 

Some,  but  not  all,  cases  are  accompanied  by  marked  anaemia. 
Neumann4  observed  a  case  in  which  the  symptoms  came  on 
acutely  and  the  red  cells  sank  to  1,120,000  x^er  cubic  millimetre. 
During  the  convalescence  which  followed  the  cells  ran  up  above 
normal,  reaching  7,700,000. 

Tschirkoff  6  reports  two  cases  in  which  the  red  cells  were  re- 
spectively 3,280,000  and  2,933,000  at  the  lowest,  but  whose 
haemoglobin  was  extraordinarily  high,  over  100  per  cent  in  one 
case.  This  he  found  on  spectroscopic  examination  to  be  due  to 
a  great  increase  of  reduced  haemoglobin  in  the  corpuscles. 
Methaemoglobin  was  also  noted. 

The  white  corpuscles   showed  no  changes,  quantitative  or 

1  Deut.  med.  Woch.,  1889,  p.  861. 

*  Zeit.  f.  klin.  Med. ,  1893,  p.  187. 

3Zeit.  f.  kliD.  Med.,  1893,  p.  266. 

4  Neumann  :  Deut.  med.  Woch.,  1894,  p.  105. 

'Zeit.  f.  klin.  Med.,  1891,  vol.  xix.,  Suppl.  Heft  37. 


OSTEOMALACIA.  321 

qualitative,  except  that  they  contained  black  pigment  granules. 
Three  cases  have  been  examined  at  the  Massachusetts  Hospital. 
The  first,  a  woman  of  thirty,  showed  6,240,000  red  cells  with 
14,000  white,  and  90  per  cent  of  haemoglobin.  The  differential 
count  of  900  leucocytes  showed  the  following  figures :  Polymor- 
phonuclear  cells,  53.4  per  cent;  lymphocytes,  41  per  cent;  eosino- 
philes,  4.5  per  cen»t;  myelocytes,  .9  per  cent. 

The  eosinophiles  were  very  large,  some  of  them  eosinophilic 
myelocytes. 

The  second,  a  man  of  forty-two,  was  very  anaemic  and  weak 
at  entrance  and  showed:  Bed  cells,  2,196,000;  white  cells, 
7,500;  haemoglobin,  20  per  cent.  Differential  count  of  200 
leucoctyes  showed:  Polymorphonuclear  cells,  65  percent;  lym- 
phocytes, 31.5  per  cent;  eosinophiles,  3.5  per  cent;  five  normo- 
blasts;  marked  poikylocytosis. 

Under  suprarenal  extract  his  blood  improved  in  a  month  till 
his  red  cells  numbered  4,700,000;  white  cells,  9,000;  haemo- 
globin, 65  per  cent. 

The  third  a  man  of  fifty-two,  showed :  October  20th — Ked 
cells,  2,848,000;  white  cells,  4,800;  haemoglobin,  45  per  cent. 
December  10th— Eed  cells,  2,624,000;  white  cells,  7,100;  haemo- 
globin, 45  per  cent.  Differential  count:  Polynuclear,  74  per 
cent;  small  lymphocytes,  22  per  cent;  large  lymphocytes,  4  per 
cent;  eosinophiles,  .4  per  cent.  No  nucleated  red  cells. 

A  fourth  patient,  kindly  sent  me  by  Dr.  Kogers,  of  Dor- 
chester, showed:  Eed  cells,  2,864,000;  white  cells,  2,000; 
haemoglobin,  51  per  cent.  Differential  count  of  300  cells 
showed:  Polymorphouuclear  cells,  63.3  percent;  lymphocytes, 
33.3  per  cent;  eosinophiles,  2.3  per  cent;  basophiles,  .3  per 
cent. 

I  have  never  seen  melanin  in  the  leucocytes  as  Tschirkoff  did 
in  his  two  cases. 

OSTEOMALACIA. 

The  blood  has  for  a  long  time  been  supposed,  on  the  author- 
ity of  v.  Jaksch  (Zeit.  f.  Jclin.  Med.,  Vol.  13,  page  360),  to  exhibit 
a  diminished  alkalinity,  the  bones  being  supposed  to  be  eaten 
away  by  acids  in  the  blood.  Von  Limbeck  and  many  other  ob- 
servers have  lately  shown  that  the  blood  is  normal  in  alka- 
lescence. 

21 


322  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

Corpuscles  and  haemoglobin  are  usually  within  normal  limits 
quantitatively,  but  Neusser  reports  an  increase  of  eosinophiles 
and  the  presence  of  myelocytes  in  the  blood. 

Ritchie1  confirms  Neusser  and  found  also  the  young  leu- 
cocytes more  numerous  than  normal. 

Fehling,2Sternberg,2  Chrobak2  found  no  increase  of  eosino- 
philes. 

Eieder's  case  was  normal  in  all  respects:  Bed  cells, 
4,892,000;  white  cells,  5,600;  eosinophiles,  3.6  per  cent;  poly- 
morphonuclear  cells,  61  per  cent. 

EICKETS. 

1.  Anaemia  is  always  present  in  severe  cases  and  often  in 
moderate  ones.     This,  together  with  the  fact  that  many  cases 
of  rickets  are  associated  with  an  enlargement  of  the  spleen,  has 
led  to  the  use  of  the  misleading  term  "  splenic  anaemia."     There 
is  no  form  of  anaemia  found  in  rickets  that  may  not  be  found  in 
other  conditions  (Morse). 

Hock  and  Schlesinger  found  an  average  of  2,500,000  red 
cells  in  a  considerable  number  of  cases  with  and  without  en- 
larged spleen. 

Von  Jaksch  describes  a  case  in  which  the  red  cells  sank  from 
1,600,000  to  750,000  within  three  months,  and  Luzet  saw  a 
similarly  rapid  process,  the  cells  falling  from  2,110,000  to 
1,596,000  within  three  weeks.  On  the  other  hand,  in  Morse's 
admirable  study  of  twenty  well-marked  cases  the  red  cells  aver- 
aged over  4,500,000  and  not  a  case  fell  below  3,500,000. 

2.  The  haemoglobin  is  always  relatively  low;  it  averaged  63 
per  cent  in  Morse's  cases,  a  color  index  of  about  .7.     Felsenthal 
got  similar  results. 

White  Corpuscles. 

It  is  often  difficult  to  say  whether  or  not  the  leucocytes  are 
increased,  owing  to  the  occurrence  of  most  cases  in  infants  at  an 
age  when  leucocytes  are  always  higher  than  in  adults— how 
much  higher  at  any  given  age  depends  largely  upon  the  degree 
of  vigor  and  forwardness  of  development  of  the  individual  child. 

In  Morse's  series,  for  example,  the  average  age  of  the  infants 

1  Edin.  Med.  Journal,  June,  1896. 

2  Cited  by  Ritchie  (loc.  cit.). 


RICKETS.  323 

is  twelve  months.  And  for  this  age  none  of  the  counts  in  his 
series  seem  to  me  necessarily  abnormal.  They  are  all  under 
16,000  except  three,  these  three  being  17,900,  18,800,  and  22,000 
respectively,  the  latter  in  a  nine  months'  infant.  Many  of  the 
counts  seem  to  me  subnormal  for  infancy  (5,500,  7,200).  Most 
observers  find  leucocytosis  present  in  many  cases,  but  not  in 
all. 

QUALITATIVE  CHANGES. 
Bed  Cells. 

As  in  all  anaemias  of  infants,  the  "  degenerative"  and  "  re- 
generative" changes  are  relatively  common. 

Polychromatophilic  forms  and  nucleated  corpuscles  are  fre- 
quently to  be  found,  the  latter  often  in  great  numbers  but  with 
a  majority  of  the  normoblast  type. 

White  Cells. 

Lymphocytosis  is  said  to  be  marked,  but,  as  with  the  ques- 
tion of  leucocytosis,  we  are  never  quite  sure  whether  the  numbers 
are  abnormal  for  that  age.,  for  lymphocytosis  is  the  normal  con- 
dition in  infants'  blood. 

When,  however,  as  in  a  case  mentioned  by  Eieder,  we  find 
75  lymphocytes  in  every  100  leucocytes,  the  child  being  four 
years  old,  we  are  surely  dealing  with  a  pathological  condition. 
Another  of  his  cases,  a  seven-months'  child,  rachitic,  with  57 
per  cent  of  lymphocytes,  seems  to  fall  within  normal  limits. 
Not  so  with  Morse's  cases.  The  highest  percentage  of  lympho- 
cytes in  his  series  was  69,  in  an  infant  of  two  months.  I  have 
similar  counts  in  health  at  that  age.  The  average  of  his  twenty 
cases  is  43  per  cent,  which  is,  if  anything,  rather  low  for  that 
age.  The  same  difficulty  arises  with  regard  to  the  reports 
of  eosinophilia  in  rickets,  since  eosinophiles  are  always  rela- 
tively numerous  in  infancy.  Morse's  highest  figure  was  7 
per  cent,  his  average  3  per  cent.  They  were  highest  in  cases 
with  splenic  tumor.  In  Rieder's  four  cases  and  in  the  three 
seen  at  the  Massachusetts  Hospital,  no  eosinophilia  was  present. 
Myelocytes  in  small  number  (.5-2.  per  cent)  are  not  uncommon, 
and  may  be  considerably  more  numerous. 


CHAPTEE  IX. 

BLOOD    DESTRUCTION    AND    HEMORRHAGIC    DIS- 
EASES. 

1.  PURPURA  HJEMORRHAGICA. 

THE  blood  is  practically  that  of  anaemia  from  hemorrhage 
(red  cells  and  haemoglobin  reduced,  white  cells  increased,  occa- 
sional nucleated  red  corpuscles  or  polychromatophilic  forms). 
Agello '  has  found  methsemoglobin  in  the  blood,  and  hence  con- 
cludes that  the  disease  is  a  poisoning  of  the  corpuscles  by 
ptomains  absorbed  from  the  intestine. 

The  blood  plates  are  much  diminished  and  may  be  entirely 
absent  in  the  worst  stages. 

Bacteria  of  various  kinds  have  been  reported  in  the  disease, 
but  negative  results  are  also  common,  and  their  presence  is 
probably  not  significant. 

The  red  cells  may  fall  as  low  as  2,500,000,  but  are  much 
oftener  slightly  or  not  at  all  diminished.  In  many  mild  cases 
there  are  no  demonstrable  blood  changes.  On  the  other  hand, 
Osier  mentions  a  case  which  sank  to  1,800,000,  and  the  loss  of 
blood  may  give  rise  to  a  fatal  anaemia  of  the  microcyte  type 
(see  page  158). 

Bensaude 2  has  observed  that  in  16  cases  characterized  by 
large  hemorrhages  (2  =  acute  "infectious,"  2  with  tuberculosis,  2 
chronic,  10= Werlhof 's  disease)  the  clot  shows  no  retraction  and 
no  transudation  of  the  serum.  Cases  with  small  hemorrhages 
(toxic,  rheumatic,  cachectic,  and  nervous)  do  not  show  any  such 
abnormal  characteristics.  Hence  he  concludes  that  at  the  outset 
of  a  case  of  purpura,  observation  of  the  clotting  process  may 
enable  us  to  foretell  whether  or  not  the  case  is  to  be  of  a  severe 
or  of  a  mild  type.  He  found  the  blood  lesion  above  described  to 

'RiformaMed.,  Napoli,  1894,  p.  103. 
2LaSemaineMed.,  1897,  p.  21. 


HEMOPHILIA. 


325 


be  greatest  during  the  hemorrhagic  crises,  slowly  disappearing 
between  them.  Hayem  has  confirmed  these  observations.  He 
finds  the  fibrin  network  almost  invisible.  Despite  this  and 
despite  the  absence  of  contraction  in  the  clot,  the  actual  rate  of 
clotting  is  normal. 

SCURVY. 

There  are  no  characteristic  blood  changes  known.  When 
hemorrhage  is  severe  the  red  cells  may  sink  very  low,  to  557,875 
in  a  case  of  Bouchut's;  Ouskow  and  Hayem  saw  counts  of 
3,500,000  and  4,700,000.  The  usual  qualitative  changes  of 
secondary  anaemia  are  present  in  severe  cases ;  haemoglobin  suf- 
fers as  usual  more  than  the  count  of  red  cells. 

Leucocytes  are  generally  increased,  whether  from  hemor- 
rhage or  from  some  complicating  inflammatory  process. 

Barlow's  disease  may  lower  the  red  cells  as  far  as  976,000— 
as  in  a  case  of  Eeinert's — the  haemoglobin  being  seventeen  per 
cent  and  the  white  cells  12,000.  This  was  the  day  before  death. 
In  any  form  of  scurvy  the  blood  plates  may  be  much  dimin- 
ished. 

HEMOPHILIA. 

The  blood  changes  are  practically  those  just  described  and 
show  nothing  characteristic  of  the  disease.  Coagulation  is 
slower  than  normal  and  blood  plates  are  sometimes  very  scanty. 
The  white  cells  are  sometimes  persistently  diminished  as  in  the 
following  cases : 

I. 


Sept.  llth. 

Sept.  14th. 

Sept.  17th. 

Sept.  20th. 

Sept.  23d. 

Sept.  24th. 

Red  cells  

2,960,000 

3  800  000 

White  cells  
Haemoglobin  

3,400 
42  per  cent. 

3,400 

3,800 

3,900 

3,700 
64  per  cent. 

3,300 
49  per  cent. 

II. 


February  8th. 

February  28th. 

4,400,000 
5,000 

30  per  cent. 

3,600,000 
5,000 

28  per  cent. 

1-  Daily  nosebleed. 

326  SPECIAL    PATHOLOGY    OF    THE    BLOOD. 


BLOOD  DESTRUCTION    (HJEMOCYTOLY8IS). 

I.  Besides  the  slow  destruction  of  corpuscles  which  takes 
place  in  any  ordinary  anaemia,  we  have  a  group  of  conditions 
under  which  a  large  number  of  red  cells  are  suddenly  destroyed 
in  the  circulation  itself.  This  may  take  place  by— 

1.  Separation  of  the  haemoglobin  from  the  corpuscles  so  that 
it  colors  the  serum. 

2.  Actual  breaking  to  pieces  of  the  red  cells  without  separa- 
tion of  the  haemoglobin. 

If  normal  blood  is  drawn  and  left  to  stand,  the  serum  which 
separates  from  the  corpuscles  is  not  red-tinged  or  but  very 
slightly  so,  provided  all  shaking  and  jarring  are  avoided.  A  very 
slight  reddish  tinge  may  appear  in  the  serum  even  with  most 
careful  technique.  In  some  condition*  the  haemoglobin,  while 
not  actually  separated  from  the  corpuscles  within  the  vessels,  is 
so  loosely  connected  to  them  that  a  considerable  quantity  sepa- 
rates post  mortem  and  colors  the  serum  in  spite  of  the  avoid- 
ance of  any  jar. 

This  condition  is  to  be  distinguished  from  true  haemoglobin- 
aemia,  in  which  the  serum  is  actually  colored  before  leaving  the 
vessels,  although  the  two  conditions  really  represent  only  dif- 
ferent degrees  of  vulnerability  of  the  red  cells. 

We  are  surer  of  a  diagnosis  of  haemoglobinaemia  when  we  find 
bits  of  broken-down  cells  in  the  fresh  blood  and  the  additional 
evidence  of  haemoglobinuria  or  jaundice. 

1.  Severe   forms   of   malaria,    yellow  fever,   typhus   fever, 
severe  forms  of  septicaemia,  and  rarely  scarlet  fever  may  cause 
haemoglobinaemia. 

2.  Paroxysmal  hcemoglobincemia,  so-called,  is  a  variety  whose 
cause  is  unknown  and  which  does  not  seem  secondary  to  any 
other  disease,  unless  a  certain  relationship  to  syphilis  be  es- 
tablished, and  to  malaria.     The  attacks  are  brought  on  by  a 
great  variety  of  causes  (cold,  muscular  or  mental  strain,  etc.). 
Some  persons  can  always  bring  on  an  attack  by  putting  the  hand 
or  foot  into  cold  water. 

Blood  Examination. 

Coagulation  is  very  rapid,  but  the  clot  soon  dissolves  again 
(Hay em).  The  fresh  blood  occasionally  shows  deformities 


BLOOD   DESTRUCTION   (H^EMOCYTOLYSIS). 


327 


in  the  corpuscles  or  bits  of  broken  cells,  and  lack  of  rouleaux 
if  examined  during  a  paroxysm.  As  a  rule  the  corpuscles  of  the 
peripheral  blood  look  normal.  Frazer  has  recently  reported  a 
case  in  which  he  excited  a  paroxysm  by  a  cold  bath  and  studied 
the  blood  with  great  care. 


Time. 

Red  cells. 

White  cells. 

Per  cent 
haemoglobin. 

Blood  plates. 

10A.M.     Before  bath  
11.05  A.M.      Twenty-five 
minutes    after   bath; 
urine  pale. 
11.45  (urine  dark)  
1  15  p  M     

4,075,000 

3,633,300 
3,760,000 
4,  200  000 

15,000 

21,800 
21.300 
21,500 

50 

50 
60 
50 

450,000 

696,000 
525,000 
4,250,000(1) 

3  45  P  M    

3,800,000 

17,700 

50 

1,600,000 

Next  day,  1  P.M  

4,100,000 

18,700 

50 

500,000 

The  enormous  increase  of  "  blood  plates"  is  striking.  It  is 
difficult  to  resist  the  conclusion  that  these  blood  plates  were  bits 
of  broken  red  corpuscles.  The  serum  was  currant-jelly  colored. 
The  appearance  of  the  corpuscles  was  quite  normal. 

All  that  is  known  of  the  disease  is  expressed  by  saying  that 
for  some  reason  the  red  cells  are  abnormally  sensitive,  so  that  any 
one  of  a  variety  of  slight  disturbances  is  sufficient  to  separate 
their  haemoglobin  and  set  it  loose  in  the  plasma. 

3.  Extensive  burns  have  been  reported  to  cause  hsernoglo- 
binsemia  with  breaking  up  of  the  red  cells,  presumably  through 
changes  in  the  serum  similar  to  those  which  make  duodenal 
ulcer  so  common  a  sequel  to  bad  burns. 

4.  Snake   poison   and  scorpion  poison   may   have    similar 
effects. 

II.  Another  group  of  corpuscle  destroyers  is  that  which 
works  by  changing  the  hcemoglobin  to  methcemoglobin.  The 
most  important  of  these  is — 

1.  Chlorate  of  Potash. — This  destroys  the  corpuscles  and  pro- 
duces hsemoglobinaemia  and  the  usual  train  of  symptoms  (jaun- 
dice, dark  urine,  etc.)  due  to  this. 

Brandenburg1  examined  the  blood  of  a  woman  who  had  taken 
two  and  one-half  ounces  of  chlorate  of  potash  in  water  the  night 
before.  The  blood  showed  marked  leucocytosis,  broken  and 
1  Berliner  klin.  Woch.,  1895,  No.  27. 


328 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


distorted  red  cells.  In  gross  it  was  chocolate-colored  and  the 
serum  after  separation  of  the  clot  was  brown.  The  red  cells 
progressively  decreased  as  follows : 

Red  cells.        White  cells. 

First  day 4,300,000        20,000 

Second  day 2,500,000 

Fourth  day 2,300,000 

Fifth  day 2,100,000 

Sixth  day 1,900,000 

Seventh  day 1.600,000        15, 000 (death). 

2.  Ehrlich  and  Lindenthal1  report  the  case  of  a  patient 
who  was  poisoned  with  nitrobenzol.  Ten  hours  after  the  blood 
was  chocolate-colored  and  showed  methaemoglobin  bands.  Un- 
der the  microscope  there  were  no  changes  till  the  third  day, 
when  poikylocytosis  appeared. 


* 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin.   - 

Nucleated 
red  cells 
per  cubic 
millimetre. 

Fifth  day 

2  275  000 

Much  increased 

55 

2,070 

Seventh  day 

1,845,000 

it             •( 

50 

7  900 

Eleventh  day  
Fifteenth  day  
Seventeenth  day  
Nineteenth  day  
"    death. 

1,600,000 
905,000 
1,102,000 
900,200 

«                    a 

44 
40 

24,700(!) 
12,000 
1,300 
540 

The  nucleated  red  cells  were  at  first  mostly  normoblasts; 
later  mostly  megaloblasts. 

3.  Antipyrin  and  antifebrin  in  doses  of  thirty  to  forty-five 
grains  may   cause  great  cyanosis    and  dangerous  prostration 
through  transformation  of  the  haemoglobin  and  methaemoglobin. 
In  certain  persons  much  smaller  doses  produce  the  same  effect. 

4.  Phenacetin  poisoning   (Kronig:    Berl.   Idin.    Woch.,   1895) 
may  cause  actual  blood  destruction  with  anaemia  in  case  the 
patient   survives  the  immediate  effects  of   the  deprivation  of 
oxygen.     A  fatal  case  of  chloral  poisoning  at  the  Massachusetts 
Hospital  showed  14,400  leucocytes  with  54  per  cent  of  haemo- 
globin. 

5.  Phosphorus  poisoning  (see  Liver,  page  290). 

6.  Workers  in  aniline  dyes  and  nitroglycerine  factories  may 

1  Zeit.  f .  klin.  Med. ,  1896,  p.  427. 


ILLUMINATING    GAS   POISONING.  329 

be  severely  poisoned  by  nitrobenzol  compounds  inhaled  and  pro- 
ducing methaemoglobinaemia. 

7.  Pyrogallic  acid  and  pyrogallol  as  used  in  treatment  of  skin 
diseases  may  lead  to  death  through  destruction  of  the  red  cells. 
Chromic  acid  (for  instance,  as  applied  through  the  vagina)  may 
have  a  similar  effect. 

Many  other  less  common  substances  work  the  same  ill-effects 
on  the  blood. 

III.  A  third  group  of  substances,  of  which  carbonic  oxide  gas 
is  the  type,  poison  by  combining  chemically  with  the  haemo- 
globin and  preventing  its  combination  with  the  oxygen  of  the 
air. 

1.  Illuminating  gas  is  for  our  purposes  the  most  important 
of  this  group. 

The  appearance  of  individual  blood  cells  is  not  altered  nor 
do  they  break  up,  but  the  corpuscles  are  useless  to  breathe  with, 
as  they  cannot  take  up  oxygen. 

The  color  of  the  blood  is  very  bright  red,  much  brighter  than 
normal. 

Eed  Cells. 

Yon  Limbeck1  found  in  two  cases  6,630,000  and  5,700,000 
respectively.  The  volume  of  these  corpuscles  (estimated  by 
Bleibtreu's  method)  was  greatly  increased,  amounting  to  70.7 
per  cent  (normal  41-48  per  cent) ,  so  that  apparently  the  size  of 
the  individual  cells  is  increased. 

Miinzer  and  Palina2  found  5,700,000  red  cells  in  one  case. 


Leucocytes. 

Eaton3  reported  four  cases,  in  all  of  which  the  white  cells 
were  increased,  the  counts  ranging  between  15,000  and  22,000 
per  cubic  millimetre. 

Miinzer  and  Palma  (loc.  cit.)  found  13,300  in  their  case. 
Twelve  such  cases  have  been  examined  at  the  Massachusetts  Hos- 
pital with  the  following  results  : 

1  Loc.  cit. ,  p.  234. 

2Zeit.  f.  Heilk.,  vol.  xv.,  p.  1. 

3  Boston  Medical  and  Surgical  Journal,  March  14th,  1895. 


330 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


ILLUMINATING  GAS  POISONING. 


Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

41 

M 

31  200 

Coma  ;  recovery. 

49 

M 

27,  100 

September  12th  ;  coma 

21 

M 

19,900 
26,000 

70 

September  13th,  entirely  well. 
Coma  ;  recovery. 

19 

M 

25,470 

97 

40 

M 

22  900 

75 

60 

M 

21,200 
15,500 
20,400 

75 

November  27th  ;  coma. 
November  29  ,  convalescent. 
Coma  ;  recovery. 

95 

M 

20,360 

110 

Death. 

45 

M 

20,100 

Coma  ;  death. 

16 

F 

18,500 

84 

Coma  ;  recovery. 

19 

M 

17  000 

December  22d 

4,930,000 

17,500 
17,000 

December  23d. 

War-then '  reports  the  same  condition  in  a  single  case.  Here 
the  specific  gravity  was  also  very  high  (v.  Limbeck  finds  that 
this  is  to  be  explained  by  the  increase  in  the  actual  size  of  the 
corpuscles) . 

When  there  is  any  doubt  as  to  diagnosis,  the  following  test 
will  settle  it :  Shake  a  small  quantity  of  fresh-drawn  blood  into 
three  times  its  volume  of  subacetate  of  lead.  If  the  blood  con- 
tains CO  the  mixture  becomes  of  a  fine  red  color;  otherwise  it 
turns  chocolate-colored." 

2.  Da  Costa  (Med.  News,  March  2, 1895)  reported  a  consider- 
able diminution  in  haemoglobin  of  patients  during  etherization, 
especially  anaemic  patients,  but  the  investigations  of  Lerber3 
do  not  confirm  this. 

Tansy  Poisoning. — A  single  case  examined  at  the  Massa- 
chusetts General  Hospital  showed:  Red  cells,  4,600,000;  white 
cells,  21,000;  haemoglobin,  70  per  cent. 

Corrosive  Poisoning  (Ammonia  Fumes). — A  patient  whose 
throat  was  covered  with  a  fibrinous  pseudo-membrane  in  conse- 
quence of  inhaling  ammonia  fumes  showed  a  leucocytosis  of 
25,800.  Red  cells  and  haemoglobin  normal. 

Opium  Poisoning  (Chronic). — The  majority  of  cases  of  the 

'  Virchow's  Archiv,  vol.  cxxxvi. 

'2  Rubner  .  Z<-it.  f.  anal.  Chemie,  xxx. ,  p.  112. 

3Inaug.  Dissert.,  Basel,  1896  (seep.  10d). 


ACUTE    ALCOHOLISM. 


331 


morphine  habit  show  normal  blood,  but  in  October,  1897,  a 
man  of  twenty-six  entered  the  Massachusetts  Hospital  for  the 
morphine  habit  who  showed  at  entrance  36,000  leucocytes 
per  cubic  millimetre.  Five  days  later  the  count  was  21,200. 
A  differential  count  of  500  leucocytes  made  on  this  day  showed : 
Polymorphonuclear  neutrophiles,  71  per  cent;  small  lympho- 
cytes, 12 ;  large  lymphocytes,  10 ;  eosinophiles,  6 ;  myelocytes, 
1.  At  the  time  of  leaving  the  hospital  he  still  showed  a  leuco- 
cytosis  of  16,400.  He  had  no  fever  and  physical  examination 
was  entirely  negative. 

Ptomain  Poisoning  (Kotten  Fish). — A  mother  and  her  four 
children  were  brought  to  the  Massachusetts  Hospital  suffering 
from  the  effects  of  decayed  fish  eaten  that  day.  The  blood 
showed  the  following :  (1),  mother:  leucoctyes,  21,600,  of  which 
95.3  per  cent  were  polymorphonuclear;  (2),  boy  of  seven  years: 
leucocytes,  19,900;  (3),  boy  of  three  years:  leucocytes,  56,800,  of 
which  92  per  cent  were  polymorphonuclear ;  (4) ,  girl  of  five  years : 
leucocytes,  32,600;  (5),  girl  of  thirteen  months:  leucocytes. 
55,400.  The  red  cells  and  haemoglobin  were  normal.  All  the 
patients  made  prompt  recoveries. 

ACUTE   ALCOHOLISM. 

It  has  been  shown  experimentally  that  in  animals  made 
drunk  with  alcohol,  there  is  an  invasion  of  the  blood  and  tissues 
by  micro-organisms  from  the  intestine.  It  may  be  that  some  of 
the  counts  here  recorded  are  thus  to  be  explained. 

ACUTE  ALCOHOLISM. 


Age. 

Sex. 

Red  cells. 

White  cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

36 

F 

15  900 

Two    weeks   drinking    hard. 

88 

M 

14  200 

74 

Temperature  102°  ;  died  ;  D.T. 
Temperature  101°. 

42 

M 

12  000 

62 

Temperature  101°  ;  D.  T. 

32 
44 

M. 
M 

3,946,000 

10,200 
9  600 

30(?) 
80 

29 
87 

F. 
M 

4,288,000 

8,000 

7  800 

55 
62 

D.  T. 

60 

F 

7  450 

65 

8?, 

M 

5  700 

88 

Autopsy 

88 

M 

5  600 

D    T 

PART  VI. 

MALIGNANT   DISEASE,    BLOOD  PARASITES, 
AND  INTESTINAL  PARASITES. 


CHAPTEE  X. 

MALIGNANT  DISEASE. 

THE  BLOOD  AS  A  WHOLE. 

1.  The  specific  gravity  is  reduced  in  most  cases,  running 
roughly  parallel  with  the  haemoglobin. 

2.  Coagulation  is  normal  or  slower  than  normal  in  uncom- 
plicated cases.     When  sloughing  and  inflammation  are  present 
it  may  be  rapid. 

3.  Fibrin  is  usually  normal;  an  increase  means  inflammation 
in  or  around  the  tumor  or  an  inflammatory  complication. 

CANCER. 
Red  Corpuscles. 

As  in  tuberculosis,  we  are  frequently  surprised  to  find  but 
little  diminution  in  the  number  of  red  cells.  In  all  but  very  ad- 
vanced cases  this  is  the  rule.  It  is  a  change  of  the  individual 
red  cells  (pallor,  loss  of  size,  of  weight,  degenerative  changes), 
rather  than  a  reduction  of  numbers. 

Nevertheless  in  the  later  cachectic  stages  of  most  cases  of 
malignant  disease,  we  do  find  a  quantitative  anaemia,  the  counts 
often  running  as  low  as  2,500,000  and  occasionally  sinking  as 
low  as  in  pernicious  anaemia.  Thus  v.  Limbeck  records  a  case 
(complicated  by  repeated  hemorrhages)  with  only  950,000  red 
cells  per  cubic  millimetre.  The  lowest  of  my  own  cases  was 
1,457,000  per  cubic  millimetre. 


CANCER.  333 

There  seems  to  be  no  considerable  difference  between  cancer 
and  sarcoma  as  regards  their  effect  on  the  red  cells.  The  fol- 
lowing table  summarizes  our  cases : 

TABLE  XXXIX.,  A.— GASTRIC  CANCER. 

Rbd  Cells. 

Between  1, 000, 000  and  2, 000, 000  4  cases. 

2,000,000    "    3,000,000 11  " 

3, 000, 000    "    4, 000, 000 23  " 

4,000,000    "     5,000,000 15  " 

5,000,000    "    6,000,000  16  " 

Over  6,000,000    3  " 

Average,  4,090,000+  72 

Nucleated  red  cells  present  in  eleven  cases  out  of  fourteen  examined. 
Normoblasts  always  in  majority.     A  few  megaloblasts  in  three  cases. 

TABLE  XXXIX.,  B. — GASTRIC  CANCER. 


Leucocytes  per  Cubic  Millimetre. 

Between    3,  000  and    4,  000  

1  case. 

4,000    "      5,000  :..    ... 

4  cases. 

5,000    "      6,000  

17    " 

6,000    "      7,000    

9    " 

•7,000    "      8,000  

8    " 

8,000    "      9,000  

8    " 

9,000    k<     10,000  

9    " 

10,000    "     12,000  

6     " 

12,000    "     15,000  

4    " 

15,000    "    20,000  

12    " 

20,000    "    30,000  .... 

5    " 

30,000    "    40,000  

3    " 

Total,  167  counts  in  86  cases. 
Average,  10,600  + 

As  will  be  seen  by  consulting  Table  XXXIX.,  A,  the 
count  of  red  cells  is  sometimes  above  normal,  doubtless  due  to 
concentration  of  the  blood  from  some  cause.  Probably  the  same 
influence  is  at  work  in  other  cases,  and  many  of  those  showing 
normal  counts  have  really  fewer  red  cells  than  they  should.  Such 
abnormally  high  counts  are  not  rare,  as  the  following  examples 
show: 


334 


SPECIAL   PATHOLOGY    OF   THE   BLOOD. 


Author. 

Case. 

Affection. 

Red  cells. 

Per  cent 
haemoglobin. 

Osterspey  *. 

1 

Cancer  of  the  stomach 

5  040  000 

80 

Osterspey  .... 
Osterspey.  .  .. 

2 
3 

Caiicer  of  the  liver  and  stomach 
Cancer  of  the  gullet  

6,184,000 
8,280  000 

87 
48 

Neubert  2  

1 

Cancer  of  the  stomach.  

5,085,000 

73 

Neubert  

2 

Cancer  of  the  liver 

4  918  000 

70 

Reinert  3  

Cancer  of  the  stomach  . 

6  200  000 

77 

I  wish  to  lay  some  stress  upon  this  point,  because  it  has  been 
stated  by  some  recent  writers  (e.g.,  Grawitz:  "Pathologie  des 
Blutes,"  Berlin,  1896)  that  the  red  cells  are  almost  always  dim- 
inished in  malignant  disease. 

The  high  counts  in  cancer  of  the  gullet  are  obviously  to  be 
explained  by  the  lack  of  liquid  taken,  the  blood  being  greatly 
concentrated  as  in  any  other  form  of  starvation. 

That  this  increase  is  not  invariably  present  (see  Table  XL., 
page  345)  is  doubtless  because  some  cesophageal  tumors  permit 
the  ingestion  of  liquid  in  normal  amounts  and  of  a  certain 
amount  of  solids. 

The  highest  counts  in  the  Massachusetts  Hospital  series  are 
in  simple  gastric  cancer  without  any  stenosis  at  either  end  of  the 
organs  (see  Cases  L,  III.,  XVI.,  and  XXL),  and  the  lowest 
count  (1,632,000)  was  in  a  similar  case  just  before  death.  Tak- 
ing all  the  cases  of  cancer  in  this  series  together,  the  average  of 
the  seventy-five  cases  at  the  time  when  treatment  began  was  4,140,- 
000  red  cells  per  cubic  millimetre. 


Haemoglobin. 

Bierfreund,4  who  has  examined  seventy-two  cases  with  re- 
gard to  their  percentage  of  coloring  matter,  found  that  in  rela- 
tively slow  and  long-standing  cases  it  averaged  68.5  per  cent, 
and  in  the  worst  cases  57.5  per  cent.  In  cases  of  mammary 
cancer  after  operation  the  haemoglobin  is  of  course  lower  owing 
to  hemorrhage,  and  Bierfreund  noticed  that  as  a  rule  the  haemo- 
globin began  to  rise  toward  normal  much  later  than  after  opera- 

1  Dissert.,  Berlin,  1892. 

2lnaug.  Dissert.,  Dorpat,  1889. 

3  "  Zahlung  d.  Blutkorp. , "  Leipzig,  1891, 

4Langenbeck's  Archiv,  vol.  xli. 


CANCER. 


335 


tions  for  non-malignant  conditions— a  week  later  on  the  average 
— and  that  it  never  reached  the  point  at  ivhich  it  ivas  before  the 
operation. ' 

The  following  table  from  Bierfreund  is  of  interest  as 
illustrating  these  points.  Cases  were  examined  before  and 
after  operation,  and  the  examinations  were  continued  daily 
after  the  operation  until  the  haemoglobin  began  to  rise 
again.  This  occurred  very  late  as  compared  with  other 
operations. 


Diagnosis. 

Per  cent 
haemoglobin 
before, 
operation. 

Per  cent 
haemoglobin 
after 
operation. 

Per  cent 
loss. 

Regeneration  time. 

Malignant     tumor     without 
complication. 
Very  large  or  rapidly  grow- 
ing tumors. 
Tumors  with  "softening"  or 
disturbances  of  function. 

68.5 
56.6 
57.5 

53 
38.4 
39.7 

15.5 

18.2 
17.8 

23     days. 
27.8  days. 
27     days. 

Total,  72  cases. 

Av.  ,  60 

Av.,42.8 

17.2 

Av.,  25.9  days. 

By  "regeneration  time"  is  meant  the  number  of  days 
elapsed  after  operation  before  the  haemoglobin  begins  to  rise. 
After  operations  for  other  causes  (non-malignant)  the  average 
regeneration  time  is  fourteen  to  twenty  days. 

It  is  very  important  that  these  results  of  Bierfreund 's  should 
be  tested.  In  Mikulicz's  surgical  clinic  at  Breslau  all  patients 
have  their  haemoglobin  tested  regularly.  In  this  country  the 
surgical  portion  of  the  profession  have  not  as  yet  taken  hold  of 
blood  examination,  and  many  questions  about  the  blood  in  sur- 
gical affections  remain  unanswered. 

Eeinbach2  examined  16  cases  and  found  the  haemoglobin  range 
between  18  to  70  per  cent,  with  an  average  of  50  per  cent. 

Eieder's3  cases  average  53  per  cent  (sarcoma  much  lower — 
see  below) . 

1  This  is  all  the  more  extraordinary  because  Bierfreund  specially  noted 
that  even  in  patients  who  gained  weight  notably  after  the  operation  the 
haemoglobin  did  not   rise  so  high  as  it  had  been  before  operation  ;   he 
watched  them  for  months  after  it.      Apparently  the  actual   presence  of 
the  tumors  is  not  the  only  cause  of  the  lack  of  corpuscle  substance. 

2  Langenbeck's  Archiv,  1893,  p.  486. 

3"Beitragez.  Kenntniss  cl.  Leucocytes  is,"  Leipzig,  1892  (Vogel). 


336  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

Laker  '  noticed  the  low  haemoglobin  percentage  in  malignant 
tumors  and  thought  it  a  help  in  excluding  benign  tumors  or 
tuberculosis,  in  which  the  haemoglobin  is  much  less  diminished. 

In  the  87  cases  of  malignant  tumors  in  which  I  have  notes  of 
the  haemoglobin  (see  tables)  the  average  is  58  per  cent.  Com- 
paring this  with  the  average  count  of  red  cells  (4,140,000),  we 
get  a  color  index  of  .65,  distinctly  higher  than  the  average  of 
chlorotic  cases,  of  which,  however,  the  figures  distinctly  remind 
us.  The  highest  cases  of  this  series  had  100  per  cent  and  90 
per  cent  of  haemoglobin  respectively,  and  the  lowest  20  per  cent 
and  22  per  cent ;  in  these  last  two  cases  the  color  indexes  were 
.36  and  .58  respectively,  not  excessively  low.  As  pointed  out 
by  Taylor  (loc.  cit.)  cases  of  malignant  disease  can  be  divided 
into  three  groups  with  reference  to  their  blood : 

1.  Those  with  approximately  normal  blood. 

2.  Those  with  a  low  haemoglobin  but  a  nearly  normal  num- 
ber of  cells. 

3.  Those  with  great  diminution  both  in  cells  and  coloring 
matter. 

Among  our  own  cases  at  the  Massachusetts  Hospital  about 
one-half  fall  under  the  second  group,  one-quarter  under  the  first, 
and  one-quarter  under  the  third. 

As  the  disease  progresses,  the  red  cells  and  haemoglobin 
steadily  go  down  (except  in  cancer  of  the  gullet),  and  at  the 
time  of  death  1,000,000  cells  per  cubic  millimetre  is  not  rare. 

The  color  index  usually  remains  below  1.  Compared  to  most 
other  varieties  of  secondary  anaemia  (e.g.,  those  in  tuberculosis 
or  nephritis)  a  quantitative  anaemia — that  is,  a  loss  of  red  cells 
as  well  as  of  haemoglobin — is  relatively  more  frequent.  In  gen- 
eral the  degree  of  anaemia  is  parallel  to  the  amount  of  cachexia, 
except  when  hemorrhage  increases  it  (as  in  tumors  of  the  stom- 
ach or  uterus). 

How  far  the  anaemia  may  be  due  to  actual  destruction  of  cells 
by  toxic  (?)  products  of  the  tumors  is  doubtful.  Grawitz  found 
that  the  injection  of  extracts  of  cancerous  tissues  caused  in 
rabbits  a  temporary  dilution  of  the  blood,  so  that  the  cells  per 
cubic  millimetre  were  diminished,  and  it  may  be  that  this  plays, 
some  part  in  the  causation  of  the  low  blood  counts. 

1  Wien.  med.  Woch.,  1886,  Nos.  18  and  19. 


CANCER. 


387 


Qualitative  Changes. 

(a)  The  average  diameter  of  the  red  cells  is  often  diminished 
either  (as  in  chlorosis)  by  a  diminution  of  the  size  of  nearly 
every  corpuscle,  or  by  a  less  general  shrinkage,  many  cells  being 
of  normal  size.     The  very  large  forms  seen  in  pernicious  anaemia 
are  rare  in  the  anaemia  of  malignant  disease,  and  never,  I  think, 
reach  the  size  of  the  giant  forms  seen  in  the  former  condition. 
Very  small  cells,  on  the  other  hand,  are  as  common   in  ad- 
vanced cases  as  in  any  other  form  of  anaemia,  except  chlorosis. 
Deformities  and  degenerative  changes  are  very  common  in  well- 
marked  cases,  often  as  great  as  in  pernicious  anaemia,  though 
they  may  be  slight  or  absent. 

According  to  Strauer,  the  deformities  found  in  malignant  dis- 
ease are  greater  than  those  found  in  any  form  of  tuberculosis, 
and  this  fact  he  thinks  of  value  in  diagnosis.  This  observation 
has  been  confirmed  by  Taylor. 

Degenerative  changes  are  sometimes  well  marked,  but  seldom, 
if  ever,  reach  so  extreme  a  condition  as  occurs  in  many  cases  of 
pernicious  anaemia. 

(b)  Nucleated  red  corpuscles  are  the  rule   in  all  advanced 
cases,  and  in  some  others.     Taylor  found  them  in  one-half  of 
the  twenty-two  cases  examined  by  him.     Malignant  disease  dif- 
fers in  this  respect  from  tuberculosis  and  most  other  conditions 
involving    secondary  anaemia,    in  that   the  nucleated  red  cells 
are  much  more  common  in  cancer  and  may  appear  even  when 
there  is  no  considerable  loss  of  red  cells  (numerically)  or  even 
when  the  haemoglobin  is  also  normal  (Schreiber).     I  have  found 
them  in  four-fifths  of  all  severe  cases  examined. 

As  a  rule  the  nucleated  corpuscles  are  of  the  norrnoblast 
types  (including  small  forms  with  dividing  nuclei) ,  but  in  very 
cachectic  cases  we  may  find  megaloblasts  as  well — always,  so 
far  as  I  know,  fewer  in  number  than  in  the  normoblasts.  This 
constitutes  one  of  the  points  of  distinction  between  pernicious 
anaemia  and  the  severest  types  of  secondary  anaemia,  such  as 
occur  in  malignant  disease.  The  megaloblasts,  when  present, 
are  in  the  minority  as  compared  with  the  normoblasts.  For 
example : 

22 


338  SPECIAL    PATHOLOGY   OP   THE   BLOOD. 

r    (Five  normoblasts.      /  ~ 

Case     I.  <  „,,  >  Seen  while  counting  400  leucocytes. 

(  Three  megaloblasts.  ) 

_   (  Two  normoblasts.      )  _ 

Case   II.  <  ^  >  Seen  while  counting  500  cells. 

(  No  megaloblasts.        J 

_    (  Five  normoblasts.       )  _, 

Case  III.  <  XT  }•  Seen  while  counting  200  cells. 

/  No  megaloblasts.        f 

Cases  could  easily  be  multiplied. 

The  characteristics  of  the  blood  changes  in  malignant  disease, 
then,  so  far  as  concerns  the  red  cells,  are  those  of  secondary 
anaemia,  which  at  times  attains  the  severest  type — but  only 
when  cachexia  is  marked,  or  when  hemorrhage  complicates  the 
disease. 

The  specific  gravity  follows  in  a  general  way  the  haemoglobin 
percentage. 

On  the  white  corpuscles  in  malignant  disease  a  great  deal  of 
interest  has  centred,  and  very  conflicting  reports  have  been 
published.  As  the  effects  of  cancer  and  sarcoma  seem  to  be 
somewhat  different  we  will  consider  them  separately. 


1.  THE  LEUCOCYTES  IN  CANCER. 
(a)   Quantitative  Changes. 

We  should  expect  great  differences  in  the  blood  of  different 
cases  if  we  consider  what  a  wide  range  is  included  between  the 
small,  hard,  slow-growing,  curable  cancer  of  the  lip  which  may 
produce  little  or  no  impairment  of  the  general  health,  and  the 
"fulminating,"  rapidly  growing  cases  with  numerous  metastases 
and  profound  prostration. 

The  former  class  of  cases  may  show  a  blood  normal  in  all 
respects,  including  a  normal  leucocyte  count;  while  in  the  latter 
the  blood  may  be  so  profoundly  altered  as  to  be  confused  with 
that  of  pernicious  anaemia  on  the  one  hand,  or  with  that  of  leu- 
kaemia on  the  other. 

In  a  general  way  it  may  be  said  that  the  more  "  malignant" 
the  cases  the  greater  the  changes  in  the  blood. 

The  effect  upon  the  leucocytes  depends  upon  the  following 
conditions : 

1.  The  position  of  the  tumor. 

2.  Its  size,  rapidity  of  growth,  and  the  number,  size,  and 
position  of  its  metastases. 


CANCER.  339 

3.  The  resisting  power  of  the  individual. 

1.  Position. — (a)  Tumors  of  the  gullet  involving  stricture  but 
not  extending  to  other  tissues  are  often  accompanied  by  a  dim- 
inution of  the  leucocyte  count,  owing  to  the  starvation  which 
they  produce.     This  is  not  true  of  all  cases,  as  is  shown  in  the 
accompanying  tables,  but  when  the  leucocytes  are  increased  there 
is  usually  an  involvement  of  other  organs  as  well. 

(b)  Cancers  of  the  uterus  and  some  of  those  of  the  stomach, 
by  reason  of  the  hemorrhage  which  they  produce,  are  apt  to  be 
associated  with  a  very  high  leucocyte  count. 

(c)  Tumors  of  the  thyroid  and  of  the  pancreas  are  said  by 
some  writers  to  cause  a  specially  great  leucocytosis.     In  my  own 
experience,  tumors  of  the  kidney  have  shown  very  marked  in- 
crease of  white  cells. 

2.  Size. — Other  things   being   equal,  the  larger  and  more 
rapidly  growing  tumors  show  in  most  cases  a  greater  leucocy- 
tosis than  small,  slow-growing  ones. 

Thus  the  cancers  of  the  lip  and  of  the  pylorus,  scirrhus  of 
the  breast  or  of  the  penis,  show  smaller  counts  than  tumors  of 
the  liver,  omentum,  and  kidney,  which  are  apt  to  grow  more 
rapidly.  Metastases  in  the  bone  marrow  are  thought  by  some 
observers  to  give  peculiar  qualitative  blood  changes  (see  below) . 

In  general,  metastases,  being  a  method  of  rapid  growth, 
simply  add  to  the  leucocyte  count. 

These  distinctions  eliminate  some  of  the  apparent  contradic- 
tions between  the  findings  of  different  individuals  who  were 
simply  describing  cancers  of  different  types.  But  even  within 
a  single  type,  there  are  very  marked  differences  in  different 
cases.  For  instance,  Alexander1  found  the  leucocyte  count  in 
cases  of  scirrhus  of  the  breast  to  vary  between  2,360  and  21,700. 
Similar  differences  have  been  reported  in  cancers  of  the  stomach 
(e.g.,  Schneider2  finding  leucocytosis  in  all  of  twelve  cases,  while 
Osterspey3  in  another  series  of  twelve  cases  found  leucocytosis 
in  only  two). 

3.  Resisting  Power. — Possibly  a  part  of  these  differences  is 
to  be  explained  by  differences  in  the  resisting  power  of  the  in- 
dividual.    But  if  this  is  so,  we  cannot  measure  the  endurance  of 
a  given  patient  by  his  general  health.     As  in  the  Civil  War  the 

1  Alexander  :  These  de  Paris,  1887. 
-Inaug.  Dissert.,  Berlin,  1888. 
3Iuaug.  Dissert.,  Berlin,  1892. 


340  SPECIAL   PATHOLOGY   OF    THE   BLOOD. 

pale,  city -bred  men  outlasted  the  healthy  farmers,  so  here  the 
tumor's  rapidity  of  growth  seems  often  to  be  greatest  in  the 
most  vigorous  young  individuals,  while  dried-up  old  women  will 
resist  its  advance  for  a  longer  period. 

We  come  now  to  the  conditions  to  be  found  in  particular 
types  of  cancerous  growth. 

Surprisingly  little  work  has  been  done  on  the  blood  in  malig- 
nant disease,  such  cases  usually  being  under  the  charge  of  sur- 
geons who  rarely  value  such  investigations.  Except  for  scattered 
counts  here  and  there,  all  our  knowledge  of  the  corpuscles  rests 
on  the  work  of  Hayem  and  Alexander  in  France,  and  Kieder,  v. 
Limbeck,  Pee,  Sadler,  Reinbach,  Osterspey,  Grawitz,  Strauer, 
Schneyer,  and  Schneider  in  Germany. 

CANCER  OF  THE  BREAST. 

Most  of  our  data  come  from  Hayem1  and  his  pupil  Alexan- 
der.2 

1.  Scirrhus  Groivths. — Number  of  cases,  14.     Average  leu- 
cocyte count,  11,400.     Highest  count,  21,700 ;  lowest,  2,360— the 
last  is  somewhat  doubtful  as  to  diagnosis ;  except  for  this  case, 
which  was  in  a  very  old,  dried-up  woman,  the  lowest  count  was 
7,400. 

In  10  out  of  the  14  cases,  the  count  was  over  10,000.  IB  the 
3  cases  seen  by  the  writer  2  showed  no  leucocytosis,  1  a  consid- 
erable leucocytosis. 

2.  Medullary  (Encephaloid)  GrowiJis. — Three  cases,  all  over 
10,000— average  11,300. 

Effects  of  Operation. 

The  following  figures  from  Hayem  are  also  of  interest : 
CASE  I. —Scirrhus  of  the  Breast. 

Before  operation 21, 700 

Five    weeks    after  operation  (wound   not 

quite  healed) 10,000 

Wound  completely  healed 6,200 

Seven  months  after  operation 8,990  (beginning  to  rise  again) 

The  growth  recurred  some  months  later  and  leucocytosis  was  again 
present. 


1  Hayem  :  "Du  Sang,"  Paris,  1889,  p.  947. 

2G.  Alexander:   "De  la  Leucocytosis  dans  les  Cancers,"  Paris  Thesis, 


1887. 


CANCER   OF   THE   STOMACH.  341 

CASE  II.  —  Scirrlms  of  the  Breast. 

First  Second 

count.  count. 

Before  operation 11, 500        11, 450 

After  operation , 8,500          6,200 

CASE  III.— Scirrhus  of  the  Breast. 

First  Second 

count.  count. 

Before  operation 11,000        12,400 

After  operation 8, 400 

CASE  IV. — Scirrhus  of  the  Breast. 

Before  operation 7,400 

After  operation 1, 300 

CASE  Y. — Medullary  Cancer  of  the  Breast.         * 

Before  operation 10, 000 

After  operation 9, 000 

Hay  em  considers'  that  by  watching  the  leucocyte  count  we 
can  predict  the  coming  of  a  recurrence  before  any  physical  signs 
are  present.  This  he  did  in  Case  I.  of  the  series  just  given. 

I  have  seen  no  confirmation  or  refutation  of  this  statement. 
It  is  one  of  the  many  points  to  which  the  attention  of  surgeons 
should  be  directed. 

CANCER  OF  THE  STOMACH. 

Here  we  have  a  much  larger  body  of  data  to  judge  from. 
Thus : 

Hayem1  in  12  cases  found  leucocytosis  present  in  5,  absent 
in  7. 

Schneider2  in  12  cases  found  leucocytosis  in  12  (all). 

Schneyer*  in  18  cases  found  leucocytosis  in  4,  and  these  4  all 
under  11,000. 

Osterspey4  in  12  cases  found  leucocytosis  in  5. 

Eieder4  in  6  cases  found  leucocytosis  in  3. 

Sadler5  in  13  cases  found  leucocytosis  in  2,  and  in  both  there 
were  complications  (abscess  of  liver,  perforation  of  gullet  with 
gangrene)  to  which  the  leucocytosis  might  be  due. 

1  "Du  Sang,"  Pa,ris,  1889,  p.  948. 

'Inaug.  Dissert.,  Berlin,  1888. 

3Inaug.  Dissert.,  Berlin,  1892. 

4  Loc.  cit. 

5  Original-Mittheilungen  aus  der  Klinik  v.  Jaksch,  1891. 


342  SPECIAL   PATHOLOGY    OF   THE    BLOOD. 

Reinbach1  iu  4  cases  found  leucocytosis  in  2. 

Eeinert 2  in  2  cases  found  leucocytosis  in  2. 

Laache3  in  5  cases  found  leucocytosis  in  none.4 

Despite  these  facts  we  have  the  record  of  a  certain  number 
of  single  cases  in  which  the  leucocytosis  has  been  enormous. 
For  instance,  Welch  in  "Pepper's  System  of  Medicine"  men- 
tioned a  case  in  which  the  ratio  of  white  to  red  cells  was  1 :  25 
(normally  1:  750  ±).  Eisenlohr's  5  case  showed  1  white  to  50 
red,  and  Potain's  6  case  showed  1  white  to  48  red  cells. 

The  Massachusetts  Hospital  series  of  86  cases  showed  leuco- 
cytosis in  30  cases  and  none  in  56  (see  Table  XXXIX.,  B). 
Out  of  those  showing  leucocytosis  10  were  under  12,500,  that  is 
the  leucocytes  were  but  slightly  increased,  leaving  only  20  out 
of  86  (or  twenty-three  per  cent)  in  which  the  leucocytosis  was 
very  marked.  Among  these  20,  the  highest  counts  were  40,000 
and  39,000,  and  the  highest  ratio  1 :  62. 

In  this  series  I  have  excluded  all  cases  in  which  there  was 
evidence  of  metastasis  in  other  organs ;  this  means  excluding  7 
cases,  6  of  which  showed  leucocytosis,  and  helps  to  account  for 
the  low  average  leucocyte  count  in  the  other  86  cases. 

In  over  three-fourths  of  these  cases  the  diagnosis  was  made 
certain  either  by  operation  or  by  autopsy ;  all  the  others  showed 
either  a  palpable  tumor  in  old  cachectic  patients  with  pain  and 
vomiting,  or  other  equally  clear  evidence  for  the  diagnosis. 
Doubtful  cases  have  been  excluded.  As  will  be  seen  by  the 
table,  in  some  of  the  cases  the  counts  were  verified  by  repeated 
examinations,  while  in  others  only  a  single  count — that  made 
when  the  patient  entered  the  hospital — was  recorded. 

As  a  rule,  the  high  leucocyte  counts  were  in  the  more  cachec- 
tic cases;  but  this  does  not  always  hold.  Cases  10,  11,  and 
28  in  Table  XXXIX.,  A,  were  very  cachectic  but  showed  no 
leucocytosis. 

The  position  of  the  tumor  in  one  or  another  part  of  the 

1  Langenbeck's  Archiv,  1893,  p.  486. 
*  LOG.  cit. 

3  "Die  Anamie,"  Christiania,  1883. 

4  Apparently,  since  he  draws  attention  to  the  fact  that  there  is  leuco- 
cytosis in  a  case  of  cancer  of  the  uterus. 

s  Deut.  Arch.  f.  klin.  Med.,  1877,  vol.  xx. 
"  Gaz.  des  Hop.,  1888,  No.  57. 


DIGESTION   LEUCOCYTOSIS   IN    CANCER    OF   THE   STOMACH.    343" 

stomach  seemed  to  have  no  connection  with  the  number  of  leu- 
cocytes. 

On  the  whole,  leucocytosis  is  relatively  infrequent  in  cancer 
of  the  stomach,  occurring  in  only  about  one-third  of  the  early 
cases.  As  the  disease  progresses  we  may  get  a  leucocytosis,  par- 
ticularly in  case  its  growth  is  rapid  and  metastases  are  frequent 
and  numerous ;  but  some  cases,  particularly  those  in  which  the 
tumor  is  small  and  grows  slowly,  may  run  their  entire  course 
without  any  leucocytosis  being  present.  In  this  respect  they 
are  like  the  majority  of  small,  slow-growing  cancers  in  other 
parts  of  the  body  (see  below). 

Hemorrhage  or  perforation  is  of  course  accompanied  by  an 
increase  in  the  number  of  white  cells — in  fact  the  highest  count 
in  the  present  series  (105,600)  occurred  in  a  case  in  which  a  can- 
cer of  the  stomach  with  metastases  in  the  liver  perforated  into 
the  peritoneal  cavity  and  started  a  virulent,  quickly  fatal  peri- 
tonitis. 

DIGESTION  LEUCOCYTOSIS  IN  CANCER  OF  THE  STOMACH. 

A  considerable  body  of  statistics  has  accumulated  to  show 
that  in  the  great  majority  of  cases  of  gastric  cancer  the  leucocy- 
tosis of  digestion  (see  above,  page  98)  does  not  occur.  B. 
Muller '  noticed  this  fact  in  5  cases  of  cancer  of  the  stomach. 
Schneyer 2  in  18  cases  found  it  invariably  absent,  while  in  3  cases 
of  benign  stenosis  of  the  pylorus  a  considerable  digestion  leuco- 
cytosis appeared,  as  was  also  the  case  in  7  out  of  8  cases  of 
ulcer  of  the  stomach,  the  exception  being  a  fatal  case. 

He  found  both  incipient  and  advanced  cases  to  be  similarly 
affected.  In  5  of  his  cases  and  in  some  of  Muller 's  HC1  was 
present  in  the  gastric  contents,  so  that  the  absence  of  digestion 
leucocytosis  was  not  due  to  absence  of  HC1. 

Hartung  (Wiener  klin.  Woch.,  p.  697,  1895)  in  a  series  of  10 
cases  (mostly  advanced)  found  no  digestion  leucocytosis,  where- 
as a  marked  increase  occurred  in  cases  of  malignant  disease  of 
other  organs. 

Capps  b  in  17  cases  examined  at  the  Massachusetts  General 

'Prag.  med.  Woch.,  1890,  No.  17. 

2Zeit.  f.  klin.  Med.,  1895,  p.  475. 

3  Boston  Med.  and  Surg.  Journal,  November  4th,  1897. 


34:4 


SPECIAL    PATHOLOGY    OF    THE   BLOOD. 


Hospital  found  a  digestion  leucocytosis  in  2,  the  increase  being 
respectively  3,270  and  3,850  cells  over  the  count  before  the  be- 
ginning of  digestion.  In  the  other  15  cases  there  was  no  in- 
crease after  a  large  proteid  meal.  Since  Dr.  Capps'  article  20 
more  cases  have  been  investigated  at  the  hospital,  in  19  of  which 
the  digestion  leucocytosis  was  absent.  Thus  in  a  total  of  37 
cases  only  3,  or  eight  per  cent,  shoived  any  digestion  leucocytosis. 
In  5  out  of  10  cases  of  chronic  gastric  catarrh  the  digestion 
leucocytosis  was  present ;  it  was  also  present  in  a  case  of  benign 
stricture  of  the  pylorus  in  a  man  of  forty-nine  on  whom  an 
operation  was  successfully  performed  later. 

Three  cases  of  ulcer  of  the  stomach  showed  marked  increase 
as  did  several  cases  of  hyperacidity  and  other  gastric  disorders 
(see  Diseases  of  the  Stomach,  page  280). 

CANCER  OF  THE  STOMACH  WITH  METASTASES. 

Most  writers  have  not  separated  the  cases  with  metastasis 
from  those  without  it.  A  glance  at  the  seven  cases  of  Table 
XXXIX.,  C,  shows  that  with  one  exception  leucocytosis  was 
present  throughout  most  of  the  disease. 

TABLE  XXXIX.,  C.— CANCER  OF  THE  STOMACH  WITH  METASTASES. 


Age. 

i 

Bed  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

48 

M. 

4,228,000 

5,000 
6,200 

70 

January  23d.    Stomach  and  liver. 
January  28th,  mealtime. 

7  300 

January  28th    three  hours  later 

41 

38 

M. 
M. 

4,272,009 
5,432,000 

10,000 
10,190 
13  653 

57 
52 

Stomach,  liver,  and  glands. 
January  6th.     Stomach  and  liver. 
January  12th. 

66 

M. 

5,  168',  030 

7,000 
14,400 
19,600 

70 
62 

January  22d,  died. 
February  14th,  no  cachexia. 
March  6th,  liver  involved. 
March  12th. 

21,640 

March  17th,  cachectic. 

Adult 

M 

3  352  000 

16  000 

Stomach    liver   and  spleen. 

54 

47 

M. 

M 

4,160,000 

24,000 
24,200 
22,500 
34,350 

60 

Stomach  and  liver. 
November  7th,  cancer  of  stomach 

30,600 

and  liver. 
November  llth. 

105,600  ! 

November  14th,  perforation  peri- 

tonitis. 

CANCEK   OF   THE   LIVER. 


345 


CANCER  OF  THE  GULLET. 

Most  authors  are  agreed  that  no  increase — in  fact  usually  a 
decrease — of  white  cells  is  the  rule  in  this  disease.  Thus  Rie- 
der  found  6,900  in  one  case;  Osterspey's  two  cases  showed  no 
leucocytosis,  and  Escherich  and  Pee  found  similar  results.1 
This  is  probably  due  to  the  fact  that  the  position  of  the  tumor, 
by  causing  starvation,  tends  to  lower  the  leucocytes,  while  it  be- 
longs to  the  class  of  small,  slow-growing  cancers  which  do  not 
as  a  rule  tend  to  produce  leucocytosis. 

Nevertheless,  two  of  the  five  cases  in  the  Massachusetts  Hos- 
pital series  (see  Table  XL. )  did  have  leucocytosis,  perhaps  owing 
to  some  metastasis  or  complication.  There  was  no  autopsy  in 
either. 

TABLE  XL. — CANCER  OF  THE  GULLET. 


No. 

Age. 

Sex. 

Red  cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

9, 

58 
46 

M. 
F 

5,488,000 

6,800 
6,800 
7  000 

100 

May  llth. 
May  18th. 
October  18th 

3 

4 
5 

51 

56 
86 

M. 

M. 
M 

2,824,000 
4,920,000 

10,600 
5,400 
6,600 
9,860 
7,600 
11,500 
8,725 
11  800 

50 

72 
30 

October  19th,  before  food. 
October  19th,  after  food. 
October  20th. 
Before  food. 
Four  hours  later. 

Hsernaturia  also 

fi 

65 

M 

11  100 

68 

7 

47 

M 

15  400 

80 

8 
9 
10 

38 
67 

38 

M 
M. 
F. 

4,604,000 
4,560,000 

15,600 
16,400 
20,600 

60 
60 
50 

During  digestion. 

CANCER  OF  THE  LIVER. 
(See  Table  XLI.) 

Ou,t  of  fourteen  cases,  leucocytosis  was  present  in  eight— a 
larger  proportion  than  in  gastric  cancer.  The  cases  were  not 
all  primary  in  the  liver  or  bile  ducts,  but  none  originated  in  the 
stomach,  and  in  all  the  greater  part  of  the  growth  was  in  the 
liver  itself. 

1  Reinbach's  two  cases  showed  a  diminution  in  the  polymorphonuclear 
cells,  which  in  all  probability  means  a  normal  or  diminished  leucocyte 
count. 


346 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


The  comparatively  great  diminution  in  the  red  corpuscles 
will  be  noted  in  the  Table  XLI.  The  condition  both  of  red  and 
white  cells  is  doubtless  due  to  the  rapid  growth  of  tumors  of  the 
liver  as  compared,  e.g.,  with  those  of  the  stomach  or  lip  (see 
below). 

TABLE  XLI.— CANCER  OP  THE  LIVER. 


Age.    j   jj 

!   OQ 

Red 
cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

55         M. 

4,170,000 

5,000 

Bile  ducts  =  starting-point.    Autopsy. 

61        M. 

3,824,000 

5,200 

52 

59 

M. 

4,570,000 

8,000 

Operated. 

72 

M. 

4,100,000 

9,000 

44 

F. 

4,953,000 
3,784,000 

7,800 
19,700 

69 
68 

January  4th,  1896.     Autopsy. 
February  12th,  1896. 

31 

F. 

4,572,000 

8,000 

62 

65 

M. 



10,300 

58 

57 

M. 

11,150 

50 

54 
50 

M. 
M. 

4,072,666 
£,200,000 

9,300 
10,800 

' 

Differential  count  of  1,000  cells:  Poly.,  82.4  per 
cent:  small  lymphocytes,  8.5;  large  lympho- 
cytes, 8.1;  old  lymphocytes,  1. 
Primary  in  bile  ducts.     Autopsy. 

y 

"M. 

4,108,000 

9,970 

45 

January 

1st,  1896. 

43 

M. 

4,160,000 

11,200 
14,100 

9 

January  3d,  1896.     Autopsy 
July  17th. 

July  19th 

.     Autopsy. 

64 

M. 

2,768,000 

15,800 

45 

May   6th 

. 

2,880,000 

21,900 

May  24th 

1,530 

45 

May  28th 

2,928,000 

11,700 

June  8th 

35 

M. 

3,800,000 

9,800 

No  vein  be 

r3d. 

22,000 

November  5th. 

Novembe 

r  6th.     Differential  count  of  500  cells: 

48 

F. 

2,900,000 

17,500 

48 

Poly.  ,  92  per  cent  ;  lymphocytes,  8.    Autopsy. 
Differential  count   of  500  cells:   Poly..  92  per 

30 

F. 

3,660,000 

17,200 

82 

cent;    lymphocytes,    5.8:     eosinophiles,    .2; 
myelocytes,  2.    Autopsy. 
Polynuclear  cells,  83  per  cent  ;  Myelocytes,  1  per 

16,800 

B  ( 

cent. 

31 

M. 

3,120,000 

18,700 

52 

December  20th. 

15,600 

Decembe 

r  30th  ;  before  food. 

14,000 

Four  hours  later. 

Adult. 

M. 

4,408,000 

25,500 

70 

50 

M. 

4,544,000 

35.600 

November  29th,  1895. 

36,400 

Decembe 

r  10th,  1896. 

3,136,000 

23,000 

January 

15th,  1896. 

4,056,000 

28,800 

February  16th,  1896.     Autopsy. 

Jan.            Feb. 

28,  000 

24 

28 

30     4 

5 

8      9 

10    11   12    13    14 

26,000 

A 

24  000 

> 

/  \ 

7 

20  000 

; 

' 

_L       A     / 

18  000 

1 

V-7-  v 

-LO,  \J\J\J 

16  000 

I 

rr 

14,000 

1 

\  j 

/ 

\l 

.  f>  f\f\(\ 

/ 

JL 

' 

X" 

V 

/ 

Died  o  1  15th 

10,000 

/ 

FIG.  36.— Chart  of  Leucocytes  in  a  Case  of  Cancer  of  the  Liver. 


CANCER   OF   THE   OMENTUM,    ETC. 


347 


CANCER  OF  THE    INTESTINE. 

Here  the  counts  range  both  high  and  low. 

Hay  em  :  found  cancer  of  the  rectum  to  show  only  9,500  leu- 
socytes.  Eeinbach 2  found  in  three  cases  of  cancer  of  the  rectum 
moderate  leucocytosis.3  Only  four  of  the  ten  cases  in  our  series 
(see  Table  XLII.)  showed  leucocytosis,  and  in  one  of  these  there 
was  a  complicating  pylephlebitis  which  probably  raised  the 
count. 

The  red  cells  show  little  change. 

TABLE  XLII. — CANCER  OF  THE  INTESTINE. 


Age. 

M 

i 

Red 
cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

56 

41 
31 
33 
59 
66 
50 
58 
34 
52 

M. 

F. 

M. 
M. 
F. 
M. 

F. 
M. 
M. 

M 

4,408,000 

5,560,000 
4,921,000 
4,368,000 
4,800,000 
4,268,000 
5,416,000 
4,160,000 

12,700 

5,800 
8,800 
5,800 
5,500 
7,150 
12,000 
15,200 
15,500 
7  400 

60 
45 

83 
33 

78 

50 
40 
55 

Cancer  of  duodenal  papilla  with  pylephlebitis. 
Autopsy. 
Cancer  of  caecum  .    Operated  successfully. 
Cancer  of  hepatic  flexure.    Operated. 
Cancer  of  colon.     Operated. 
Cancer  of  caecum.    Autopsy. 
Cancer  of  intestine  (where  ?J». 
Cancer  of  rectum. 
Cancer  of  rectum  (operation). 
Metastases,  pi  imary  in  sigmoid. 

47 

F 

9  300 

63 

28 
52 

M. 
M. 

2,424,000 
2,440,COO 

5,300 
7,800 
6,800 

72 

Cancer  of  caecum.     Operation. 
Cancer  of  caecum. 
No  digestion  leucocytosis. 

CANCER  OF  OMENTUM  AND   ABDOMINAL  ORGANS 
GENERALLY. 

The  nine  cases  seen  at  the  Massachusetts  General  Hospital 
in  which  cancerous  tissue  was  pretty  generally  distributed 
through  the  abdominal  organs,  all  showed  leucocytosis  with  two 
exceptions  (see  Table XLIIL,  A). 


1  Loc.  cit. 

2  Loc.  cit. 

3  Apparently — that  is,  the  percentage  of  adult  cells  was  increased, 
did  not  count  the  leucocytes  as  a  whole. 


He 


348 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


TABLE  XLIIL,  A.— CANCER  OF  OMENTUM  AND  ABDOMINAL  ORGANS 

GENERALLY. 


Age. 

M 

i 

Red 
cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

50 

F 

Greatly 

Markedly 

48 

M 

increased. 

7  250 

diminished. 

of  400  cells:  Poly.  ,'84.5  per  cent;  small 
lymphocytes,  8;  large  lymphocytes,  5; 
eosinophiles,  2.5.     Autopsy. 
May  13th 

6,500| 

May  20th     No  digestion  leucocytosis 

42 

26 

M. 

M 

4,560,000 

7,300  f 
7,800 

10,600 
9  000 

60 

October  13th.     Poly.,  88  per  cent;   lym- 
phocytes, 10;  eosinophiles,  2. 
October  16th. 

65 
Adult 

M. 

M 

3,772  000 

11,700 
13700 

Adult. 

F 

5,500,000 

26,200 

Autopsy 

45 

F 

27400 

Adult 

M 

Greatly 

Markedly 

Differential  count  of  500  cells*   P'oly     80 

increased. 

diminished. 

percent;  lymphocytes,  20. 

CANCER  OF  THE   KIDNEY. 

Of  five  cases  which  I  have  examined  (see  Table  XLIIL,  B)  all 
showed  very  large  leucocyte  counts— viz.,  25,000,  27,000,  28,500, 
43,100,  82,000,  and  91,000,  an  average  of  54,000.  In  three  of 
these  cases,  however,  the  tumors  may  have  been  sarcomata,  as 
no  microscopic  examination  was  made.  Most  of  the  cases  had 
fever,  chills,  and  signs  of  inflammation,  which  may  account  for 
part  of  the  leucocytosis. 


TABLE  XLIIL,  B. — CANCER  (OR  SARCOMA)  OF  KIDNEY. 


Age. 

y, 
<a 
& 

Red 
cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

53 

M. 

4,312.000 

25,000 

32 

Differential  count  of  800  cells:    Poly.,  80.9  per 

cent;    lymphocytes.    15.8;    eosinophiles,    3.3- 
No  nucleated  red  cells. 

2 

F. 

3,756,000 

27,000 

Differential   count   of  500  cells:    Poly.,    66  per 
cent;     lymphocytes,    29.5:     eosinophiles,    2; 

myelocytes,    2.5;    normoblasts,  24;    megalo- 

blasts,  2.     Autopsy. 

57 

F. 

5,200,000 

28,500 

Supposed  leukaemia.     Differential  count  of  500 

cells:    Poly.,   81.8  per  cent;    small  lympho- 

cytes,   12;     large   lymphocytes,  4.2;   eosino- 

philes, 2.     Autopsy. 

49 

F. 

3,360,000 

43,100 

Supposed     leukaemia.       Differential    count    of 

1,000    cells:    Poly.,   92.9  per  cent:    lympho- 
cytes,  6.2;    myelocytes,  .9;    normoblasts,  2; 
megaloblasts,  1.    Autopsy. 

50 

F. 

4,111,000 

82,000 

July  8th. 

2,780,000 

91,000 

Poly.,  98  per  cent;  lymphocytes,  2. 

CANCER    OF   UTERUS. 


349 


Yon  Limbeck's '  case  mounted  steadily  from  18,514  to 
80,541. 

CANCER  OF  THE  UTERUS. 

In  six  cases  Hayem  a  found  no  increase — the  counts  ranging 
from  4,575  to  9,500  with  an  average  of  7,800. 

RLeder,8  on  the  other  hand,  in  a  single  case  found  30,800,  and 
the  three  cases  counted  at  the  Massachusetts  Hospital  showed 
respectively  19,400,  22,250,  and  34,900  (see  Tables  XLIV.,  A 
andB). 

There  is  need  of  more  data  on  this  subject. 


TABLE  XLIV.,  A.— CANCER  OF  THE  UTERUS. 


1 

Age. 

M 

£ 

Red 
cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

2 

3 
4 

48 
51 

31 
|     ,8 

F. 
F. 

F. 
F. 

2,696,030 
3,232,000 

19,400 
30,700 
34,900 

22,250 
20,170 

20 

27 

October  2Gth. 
October  28th. 
Differential  count  of  1,000  cells:  Poly.,  88  per 
cent;     small  lymphocytes,    11.7;     eosino- 
philes,  .2;  myelocytes,  .1.  Two  normoblasts. 

Ureter  blocked  ;  anuria  nine  days.   Autopsy 

2,889,680 

75 



TABLE  XLIV.,  B.— CANCER  OF  THE  OVARY. 


£ 

Age. 

fl 

02 

Red 

cells. 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

1 

i> 

36 

F. 

F, 

4,500,000 
3.248.000 

25.000 
32.800 

62 

Operation. 
Operation. 

CANCER  OF  THE  PROSTATE. 

1|      45      JM.  |    |     10,200     |  | 

CANCER  OF  THE  LIP. 

1  I      51      |  M.  |  7,000,000  |      6,300     |  | 

CANCER  OF  THE  BREAST. 


31 
f 

F. 
F. 

6,000,000 

8,000 
Not 

Differential  count  of  600  cells:    Poly.,  72.4 

increased 

per  cent;  lymphocytes,  25.4;  eosinophiles. 

2.2. 

? 

F. 

Marked 



Differential  count  of  400  cells:  Poly.,  89  per 

increase. 

cent;  lymphocytes,  11. 

CANCER  OF  THE  NECK. 

42 

M. 

Marked 

Poly.,  88.5  per  cent. 

increase. 

Loc.  cit. 


2  Loc.  cit. 


3  Loc.  cit. 


350  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

TABLE  XLIV. ,  B  (Continued). — CANCER  OF  THE  PANCREAS. 


£ 

Age. 

X 

£ 

Red 

cells, 

White 
cells. 

Per  cent 
haemo- 
globin. 

Remarks. 

•J 

54 

M 

18300 

70 

Metastases 

2 

56 

M 

17,600 

Liver  and  spleen  also 

8 

64 

M. 

15,900 

General  peritonitis. 

CANCER  OF  VERTEBRJE. 

62   |F.  |  |  13,200  |  | 

ADENOMA  OF  THE  SUPRARENAL  BODY. 

59      |  M |     24,200         Autopsy. 


Cancer  of  the  Up  has  apparently  been  neglected  so  far  as 
blood  examination  is  concerned.  Hayem,  Kieder,  and  Keinbach 
give  but  one  case  each,  the  counts  being  respectively  7,000,  11,- 
600,  and  "not  increased."  In  a  single  case  at  the  Massachu- 
setts Hospital  I  found  6,300. 

The  following  scattered  counts  may  be  added:  Cancer  of 
tongue,  7,000  (Hayem);  cancer  of  scrotum,  6,700  (Hayem); 
cancer  of  navel,  7,100  (Hayem);  cancer  of  larynx,  7,200 
(Hayem),  16,000  (Keinbach);  cancer  of  ovary,  25,000  (Massa- 
chusetts Hospital)  and  "no  increase"  (Eeinbach);  cancer  of 
neck,  20,000  (Massachusetts  Hospital)  and  "no  increase"  (Eein- 
bach); cancer  of  pancreas:  Hayem,  2  cases — 9,400  and  9,900; 
Schneider,  1  case — 12,000;  cancer  of  vagina,  9,800  (Eieder) ; 
cancer  of  penis,  7,000  (Hayem);  cancer  of  thyroid,  70,000 
(Hayem)  (a  very  rapidly  growing  tumor) ;  cancer  of  media- 
stinum, "marked  increase"  (Eeinbach);  cancer  of  prostate,1 
10,200. 

Qualitative  Changes  in  the  Leucocytes. 

1.  The  percentage  of  polymorphonuclear  neutrophiles  is 
usually  high  in  cases  with  leucocytosis  and  normal  in  those 
without  it.  This  rule  holds  for  perhaps  three-fourths  of  the  cases, 
but  there  are  many  exceptions  to  it.  For  instance,  Taylor2 
reports  27,840  leucocytes  with  65.6  per  cent  polymorphonuclear 
cells,  14,800  leucocytes  with  66.2  per  cent  polymorphonuclear 

1  Braun  (Wien.  med.  Woch.,  1896,  p.   582)  mentions  a  cancer  of  the 
prostate  in  which  the  leucocytosis  instead  of  being  made  up  mostly  by  the 
adult  leucocytes,  was  associated  with  a  large  increase  of  the  small  lympho- 
cytes together  with  numerous  eosinophilic  myelocytes. 

2  Taylor:  Internat.  Med.  Mag.,  July,  1897. 


THE   BLOOD    IN   CANCER.  351 

cells,  25,000  leucocytes  with  58.2  per  cent  polymorphonu- 
clear  cells,  45,000  leucocytes  with  43.7  per  cent  polymorpho- 
nuclear  cells,  the  last  a  marked  lymphocytosis.  On  the  other 
hand,  he  found  88.7  per  cent  of  the  polymorphonuclear  cells  in 
a  total  leucocyte  count  of  3,000.  My  own  experience  is  similar 
—i.e.,  88  per  cent  of  polymorphonuclear  cells  with  a  total  count 
of  7,800  leucocytes,  though  I  have  never  seen  so  marked  a 
lymphocytosis  as  was  present  in  'Taylor's  cases.  He  also 
noted  a  relative  increase  in  the  large  lymphocytes  which  my 
counts  have  not  shown. 

Keinbach  found  in  8  cases  with  leucocytosis  89  per  cent  in 
2  cases  and  87,  86,  83,  81,  80,  and  77  per  cent  in  others.  In 
the  Massachusetts  General  Hospital  series  the  following  per- 
centages occurred:  When  no  leucocytosis  was  present  88.7,  88, 
86,  79,  66,  62.5,  62,  60,  57  per  cent,  etc.  With  leucocytosis, 
96,  98,  92,  90,  90,  88,  87,  86,  84,  83,  74  per  cent,  etc.  (See 
Tables  XXXIX. ,  XLL,  XLIIL,  XLIV.). 

2.  Eosinop Idles  are  not  always  notably  decreased  (as  they  are 
in  many  other  leucocytoses)  nor  are  they  increased  except  when 
bone  metastasis  occurs  (see  below).     In  Keinbach 's  16  cases  the 
average  percentage  was  2  +  per  cent.     In  the  Massachusetts  Hos- 
pital cases  the  average  was  1.2  per  cent,  but  in  7  of  the  38  cases 
in  which  differential  counts  were  made,  no  eosinophiles  were 
seen. 

3.  Myelocytes. — Perhaps  more  commonly  than  in  other  con- 
ditions except  leukaemia  and  pernicious  anaemia,  we  find  in  ma- 
lignant disease  small  percentages  of  myelocytes,  as  the  following 
cases  show : 

CASE  I. — Extensive  abdominal  cancer;  great  cachexia.  Six 
hundred  cells  showed: 

Polynuclear  neutrophiles. ..   89.4  per  cent 

Lymphocytes 10. 

Eosinopbiles 1        " 

Myelocytes  (3  in  600  cells)    5       " 

CASE  II. — Cancer  of  uterus;  marked  cachexia  and  leucocy- 
tosis. One  thousand  cells  showed : 

Poly  nuclear  neutrophiles 82.3  per  cent. 

Lymphocytes 17.3       " 

Myelocytes  (4  in  1,000  cells) 4 

CASE  III. — Cancer  of  uterus;  died  two  days  later.     Eed  cor- 


352  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

puscles,  7,000,000;  white,  62,000.     Considerable  stasis  helps  to 
explain  the  count.     Differential  count  of  500  cells  showed : 

Poly  nuclear  neutrophiles 93  per  cent. 

Lymphocytes 6          " 

Eosinophiles 0         " 

Myelocytes  (5  out  of  500) 1         " 

CASE  IV. — Cancer  of  liver,  jaundice  and  cachexia;  died  soon 
after.  Differential  count  of  500  cells  showed : 

Poly  nuclear  neutrophiles 92.    per  cent. 

Lymphocytes.    6.          " 

Small  myelocytes. 1.2        " 

Large  myelocytes  (4  in  500) 8       " 

CASEY. — Cancer  of  abdomen ;  cachectic.  Differential  count 
of  1,000  cells  showed: 

Polynuclear  neutrophiles 82.    per  cent. 

Lymphocytes 16.6       " 

Eosinophiles 1.          " 

Myelocytes  (4  in  1,000) 4.          " 

CASE  VI. — Cancer  of  stomach,  liver,  etc.,  with  perforated 
stomach;  cachexia.  Leucocytes,  105,000.  Fifteen  hundred 
cells  showed : 

Polynuclear  neutrophiles 90. 7  per  cent. 

Lymphocytes , 4. 8       " 

Eosinophiles .2        " 

Myelocytes  (68  in  1,500) 4.3 

CASE  VII. — Cancer  of  uterus ;  cachexia.  In  1,000  cells  there 
were: 

Polynuclear  neutrophiles 88.    per  cent. 

Lymphocytes 11,7       " 

Eosinophiles .2        " 

Myelocytes 1 

CASE  VIII. — Cancer  of  kidney;  great  cachexia.  In  1,000 
cells  there  were : 

Polynuclear  neutrophiles 92.9  per  cent. 

Lymphocytes 6. 2       " 

Myelocytes , 9 


SARCOMA.  353 

CASE  IX. — Cancer  of  kidney ;  great  cacliexia.  Leucocytes, 
27,000.  Five  hundred  cells  showed: 

Polymiclear  neutrophiles 66.    per  cent. 

Lymphocytes 29.5        " 

Eosinophiles 2.          " 

Myelocytes 2.5       " 

CASE  X.  — Cancer  of  liver.     Five  hundred  cells  showed : 

Polynuclear  rieutropniles 92.    per  cent. 

Lymphocytes 5. 8       " 

Eosinophiles 2       " 

Myelocytes 2.          " 

About  one-half  of  all  the  cases  of  cancer  examined  by  me 
have  shown  myelocytes. 

Epstein  (Wiener  med.  Presse,  December,  1894)  in  a  case  of 
cancer  with  metastatic  bone  nodules  noticed  large  numbers  of 
nucleated  corpuscles  (normoblasts  and  megaloblasts)  and  mye- 
locytes, but  I  think  the  association  was  a  mere  coincidence,  since 
I  find  that  myelocytes  and  erythroblasts  are  very  commonly 
present  in  cacliexia  from  any  cause. 

SARCOMA. 

In  general  the  effects  of  sarcoma  are  like  those  of  cancer,  but 
worse.  Great  anaemia  and  higher  leucocyte  counts  are  the  rule. 
The  literature  of  the  subject  is  rather  scanty. 

Red  Cells. — Hay  em  in  a  case  of  osteosarcoma  counted  the 
r^d  cells  at  663,400  per  cubic  millimetre. 

Laker1  describes  an  "  abdominal  cystosarcoma"  in  which  two 
counts  of  red  cells  showed  2,800,000  and  2,500,000. 

Yon  Limbeck2  in  1  case  found  1,118,000,  and  in  another  2,- 
240,000.     Both  were  osteosarcomata. 

Sadler3  in  3  cases  found  2,710,000,  3,637,000,  4,500,000. 

Riecler*  in  3  cases  (all  osteosarcomata)  found  1,846,160,  3,- 
770,000,  and  3,995,000. 

The  Massachusetts  Hospital  blood  counts  include  15  cases 
in  which  the  red  cells  were  counted  (see  Table  XLY.,  A  and  B), 
the  average  being  4,400,000,  not  nearly  so  low  as  that  recorded. 

1  Wien.  med.  Woch.,  1886,  p.  926. 

2  Loc.  cit.,  p.  343. 

3  Loc.  cit. ,  pp.  88,  3D. 

4  Loc.  cit.,  pp.  98,  100. 
23 


354 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


by  other  observers;  still  low  counts  occurred  (2,706,000,  2,637,- 
000,  3,842,000). 

The  qualitative  changes  in  the  red  cells  consist  (as  in  cancer) 
of  the  "degenerative"  changes  (deformities  in  size  and  shape, 
englobular  changes)  present  in  marked  cases,  and  the  presence 
of  nucleated  corpuscles,  when  cachexia  is  marked. 

TABLE  XLV.,  A. — SARCOMA  WITH  LEUCOCYTOSIS. 


Age. 

M 
£ 

Red 
cells. 

White 
cells. 

Per 
cent 
haemo- 
globin. 

Remarks. 

4,188,000 

98000 

Polynuclear  cells,  90.  2  per  cent 

4312000 

25  000 

32 

Polynuclear  cells,  80  9  per  cent 

4,000,000 

44,600 

42 

Polynuclear  cells,  70  per  cent  (infant  of  twenty 

21 

F 

2  706  000 

56  000 

months). 
Sarcoma  of  kidney     Autopsy 

35 

F. 

4,560,000 

17,000 
23900 

65 

Melanotic  sarcoma  all  abdominal  organs  (bone 
metastasis  ?).     November  30th,   1895.     Differ- 
ential count  of  600  cells:    Poly.,  71  per  cent; 
small  lymphocytes,  11  ;  large  lymphocytes,  5.2; 
eosinophiles,  12.4(1);  myelocytes,  4. 
December    7th 

33,400 
37,900 
41,200 
33  000 



December  13th. 
December  19th. 

December  22d 

36,000 

December  26th 

40200 

January  14th 

46 

M 

4700000 

55,400 
16000 

January  28th. 
Sarcoma  of  abdominal  organs 

19  000 

Three  days  later     Autopsy 

32 

24 

M. 

M 

2,630,000 
2,900,000 
4,352,000 

24,000 
21,000 
13600 

50 

General  sarcomatosis. 
One  week  later.     Autopsy. 
Sarcoma  of  kidney. 

41 
68 

M. 
F 

3,842,000 
6,200,000 

61,100 
16,000 

55 

Sarcoma  of  lung,  etc.    Autopsy. 
Sarcomatosis. 

48 

M 

Marked 

Differential  count  of  700  cells  •  Poly    70  per  cent  • 

57 

M. 

4,180,000 

in- 
crease. 

13,000 
16250 

47 

lymphocytes,  22  ;   eosiuophiles,  1  ;  myelocytes, 
7.     Sarcomatosis. 
Melanotic  sarcoma  of  abdominal  organs. 
One  week  later 

Adult. 

M 

15,180 
18,000 

Sarcoma  of  abdominal  organs. 

Great 

Osteosarcoma  (thigh)      Differential  count  of  500 

1 

in- 
crease. 
Great 

cells:   Poly.,  74  per  cent;  small  lymphocytes, 
19;  large  lymphocytes,  6;  eosinophiles,  1. 
Sarcoma    of    abdominal    organs       Differential 

in- 
crease. 
13  200 

count  of  800  cells  :  Poly.  ,  84  per  cent  ;  lympho- 
cytes, 15.5;  eosinophiles,  5. 

36 

M. 

6,700 

TABLE  XLV.,  B.— SARCOMA  WITHOUT  LEUCOCYTOSIS. 


Per 

Age. 

Red 

cells. 

White 
cells. 

cent 
haemo- 

Remarks. 

1 

globin. 

29 

M. 

5,280,000 

8,200 

Sarcoma  of  testicle. 

37 
? 

F. 
M. 

4,980,000 
4,946,000 

9,000 
9,000 

78 

Sarcoma  of  ovary. 
Osteosarcoma  of  shoulder. 

24 

M 

4,952,000 

6,000 

Small  recurrent  sarcoma  of  groin. 

Small  tumors  are  often  without  any  effect  on  the  blood  (see 


SARCOMA. 


355 


Table  XLV.,  B).  According  to  v.  Limbeck1  this  is  oftener  true 
than  in  cancer. 

Hemoglobin.—  KeinbachV  20  cases  ranged  between  23  and  75 
per  cent,  averaging' 52  per  cent. 

Bierfreund  3  in  29  cases  found  variations  between  40  and  75 
per  cent. 

Von  Limbeck's  2  cases  had  28  and  48  per  cent  respectively. 

Kieder's*4  cases  showed  at  the  beginning  of  treatment  29, 
56,  57,  and  65  per  cent  respectively,  but  in  1  case  the  haemoglobin 
went  down  gradually  while  under  observation  until  it  reached 
6  per  cent  (!),  the  lowest  point,  Eieder  says,  that  he  has  ever 
seen  in  any  disease. 

Sadler's5  cases  showed  33,  45,  and  78  per  cent. 

In  the  5  cases  of  Table  XLV.  in  which  this  point  was  noted, 
the  average  is  58  per  cent. 

On  the  whole,  the  coloring  matter  seems  to  be  more  dimin- 
ished than  in  most  cases  of  cancer. 

Leucocytes.— The  following  tables,  slightly  modified  from 
v.  Limbeck,  show  the  important  points. 


No. 

Observer. 

Diagnosis. 

Count. 

1  . 

Hay  em. 

Osteosarcoma. 

11  250 

2  

Alexander. 

52  700 

3 

16  430 

4 

16  275 

5  

17,050 
15  900 

6 

15,570 
13  020 

7 

10  950 

8  .. 

12,090 
11  248 

9  

Rieder. 

12  700 

10 

10,900 
9  100 

11 

8  000 

12  

v  Limbeck 

32  000 

13  .. 

u 
Reinhach. 

26,800 
20,  000 

14 

u 

13  000 

15 

Massachusetts  Hospital 

21  000 

16 

u 

9  000 

Average, 

17,000  ± 

1  Loc.  cit. 
4  Loc.  cit. 


2  Loc.  cit. 
5  Loc.  cit. 


3  Loc.  cit. 


356 


SPECIAL   PATHOLOGY    OF   THE   BLOOD. 


No. 

Observer. 

Diagnosis. 

Count. 

1 

Hay  em. 

Lymphosarcoma. 

11,700 

2            

Alexander 

19,910 

3        

19,530 

4    

11,696 

5  

11,470 

6 

10  540 

7                      .    . 

v.  Limbeck 

55  100 

8 

38  000 

9  

10  800 

10  

Sadler. 

33,  248 

11  

19,299 

12  

9,044 

Average, 

20,000-f 

No. 

Observer. 

Diagnosis. 

Count. 

1  ., 

Rieder. 

Melanosarcoma. 

41,600 

2 

28  500 

3 

u 

22  300 

4    ...    . 

Reinbach. 

25  000 

5  

u 

8  000 

6  

Massachusetts  Hospital 

37  900 

7  

u                           u 

13,000 

Average, 

25,  100  -f 

For  other  sarcomata,  see  Table  XLY.,  A  and  B. 
On  the  whole,  leucocytosis   appears  to  be  more  constant  and 
of  greater  extent  in  sarcoma  than  in  cancer. 

Qualitative  Changes. 

1.  The  increase  of  polymorphonuclear  leucocytes  which  we 
find  in  most  forms  of  leucocytosis  is  not  always  present  in  sar- 
coma '  and  seems  to  be  less  frequent  than  in  cancer  (see  Cases 
5,  11,  14,  Table  XLY.) 

As  in  cancer,  it  may  be  present  when  no  increase  in  the  total 
leucocyte  is  to  be  found,  and  may  be  the  only  indication  of  any 
disease  in  the  organism. 

2.  A  few  cases  are  on  record  in  which  a  large  percentage  of 
eosinophiles  has  been  present. 

Reinbach  found  48  per  cent  of  eosinophiles  in  a  case  of  sar- 
coma of  the  neck  with  sloughing  and  ulcerative  endocarditis,  the 

1  Palma  (Deut.  Med.  Woch. ,  1892)  reports  lymphocytosis  in  sarcoma. 


SARCOMA. 


357 


percentage  continuing  over  40  for  several  weeks.1  Autopsy 
showed  sarcomatous  nodules  in  the  bone  marrow.  In  another 
case,  a  tumor  of  the  abdomen,  the  eosinophiles  were  10.5  per  cent, 
and  in  two  others  8  per  cent. 

A  case  of  apparent  sarcoma  of  the  abdominal  organs  (no 
autopsy)  at  the  Massachusetts  General  Hospital  in  January, 
1896,  had  12.4  per  cent  of  eosinophiles. 

Such  cases  should  certainly  make  us  think  of  bone  metas- 
tases,  and  Neusser  speaks  of  osteosarcomata  as  being  accom- 
panied by  eosinophilia,  but  the  evidence  is  as  yet  fragment- 
ary. 

3.  Myelocytes. — Keinbach's  case  just  described  had  a  low  per- 
centage of  rnyelocytes. 

The  following  cases  illustrate  the  same  point : 

CASE  I.  is  a  case  of  sarcomatosis  in  a  man  in  whom  sarcoma- 
tous nodules  were  distributed  all  over  the  internal  organs  and  in 
the  skin.  A  differential  count  of  700  white  cells  showed  in  his 
case: 

Typical  myelocytes  (over  15^) 2  per  cent. 

Small  myelocytes  (under  15/*) 5        " 

Lymphocytes 22        " 

"  Polynuclear  neutrophiles" 70        " 

Eosinophiles 1        " 

The  autopsy  showed  no  special  lesions  in  the  spleen,  glands, 
or  bone  marrow,  except  those  due  to  the  sarcomatous  nodules. 

1  The  full  counts  are  as  follows : 


April  4th, 

1892. 

May  20th,  18 

tt, 

Red  cells 

5  396  000 

Red  cells 

4  512  000 

White  cells 

120  000  (') 

White  cells 

52  000 

Haemoglobin. 

60  per  cent 

Haemoglobin  

55  per  cent. 

DIFFERENTIAL  COUNTS. 


April  4th. 

May  1st. 

May  20th. 

May  26th. 

Poly,  neut 

Per  cent. 

48 

Per  cent. 
51 

Per  cent. 

664- 

Per  cent. 
51  4- 

Eosinophiles  .  . 

48 

46 

42 

444- 

Lymphocytes  .... 

2  7 

2  32 

1  5 

3.2 

Myelocytes  

1 

.68 

.64 

.8 

358  SPECIAL  PATHOLOGY  OF  THE  BLOOD. 

CASE  II. — Sarcoma  of  abdominal  wall.  Differential  count  of 
800  cells  showed : 

Poly  nuclear  neutrophiles 84.    per  cent. 

Ly  mphocy  tes 10. 5       " 

Large  lymphocytes 5.          " 

Eosinophiles 2       " 

Myelocytes 3 

CASE  III.  (No.  2,  Table  XLV.,  A).— Six  hundred  cells  con- 
tained : 

Polynuclear  neutrophiles 71.    per  cent. 

Lymphocytes 16.2       " 

Eosinophiles 12.4       " 

Myelocytes 4       " 

Summary  of  Blood  Changes  in  Malignant  Disease. 

1.  Small,  slow-growing  tumors  and  the  early  stages  of  all 
tumors  may  have  no  effect  on  the  blood  appreciable  by  our 
present  methods  of  examination. 

2.  In  advanced  cases  the  red  corpuscles  often  become  thin, 
light,  and  pale,  and  finally  their  number  may  be  greatly  de- 
creased, the  counts  running  sometimes  as  low  as  in  pernicious 
anaemia.     In  this  respect,  as  in  others,  sarcomata  seem  to  in- 
jure the  blood  more  than  cancers. 

3.  The  color  index  is  always  below  1,  but  is  rarely  as  low  as 
we  find  it  in  severe  chlorosis. 

4.  Normoblasts   and  megaloblasts   (the  latter  being  in  the 
minority)  may  occur,  the  former  even  in  the  absence  of  severe 
anaemia.     Deformities  in  size  and  shape  are  common. 

5.  Leucocytosis  is  present  in  the  cachectic   end-stages  of 
many  cases,  but  is  frequently  absent  in  small  tumors  of  slow 
growth  and  without  metastases.     The  polymorphonuclear  cells 
are  often  relatively  increased. 

6.  Fibrin  is  not  increased. 

Diagnostic  Value. 

1.  When  we  are  dealing  with  an  obscure,  deep-seated  dis- 
ease, if  hemorrhage  is  excluded,  the  presence  of  persistent  leuco- 
cytosis  suggests  suppuration  or  malignant  disease  (rather  than 
tuberculosis  or  syphilis,  for  example),  and  excludes  any  simply 


MALIGNANT   DISEASE.  359 

functional  or  hysterical  affection.  The  absence  of  leucocytosis, 
however,  does  not  exclude  malignant  disease,  though  it  makes 
suppuration  very  unlikely. 

2.  Between  malignant  disease  and  suppuration — if  the  other 
signs  and  symptoms  do  not  decide — there  may  be  nothing  in  the 
blood  to  decide.     In  decided  pyaemia  we  may  get  pyogenic  cocci 
from  the  blood  by  culture,  but  a  negative  result  would  not  ex- 
clude the  suppurating  focus. 

The  absence  of  any  increase  of  fibrin  in  the  blood  speaks 
against  suppuration,  and  therefore  in  favor  of  malignant  disease ; 
but  the  presence  of  increased  fibrin  network  is  not  decisive  either 
way,  as  it  may  be  met  with  in  connection  with  neoplasms, 
though  more  common  in  suppuration. 

3.  Between  malignant  disease  and  hemorrhage — a  marked 
anaemia  favors  the  latter,  provided  the  case  is  a  recent  one ;  for 
the  anaemia  of  malignant  disease  is  comparatively  slow  to  develop. 
The  leucocytes  give  no  help. 

4.  Between  cancer  and  ulcer  of  the  stomach,  if  there  has  been 
no  recent  hemorrhage,  leucocytosis  favors  cancer;  but  its  absence 
is  of  no  weight  either  way. 

The  haemoglobin  is  said  to  decrease  steadily  in  cancer,  while 
in  ulcer  it  tends  to  return  toward  normal  after  the  cessation  of 
hemorrhage. 

The  presence  and  persistence  of  digestion  leucocytosis 
speak  against  cancer,  and  its  absence  in  favor  of  cancer.  It 
must  be  remembered,  however,  that  any  variety  of  catarrh  or 
dilatation  (should  such  be  present)  can  also  prevent  digestion 
leucocytosis,  and  that  the  latter  is  not  invariably  present  even  in 
health. 

5.  Between  cancer  of  the  liver  or  bile  ducts  on  the  one  hand 
and  simple  gall-stone  colic  or  gall-stone  obstruction,  the  presence 
of  leucocytosis  favors  cancer.     As  usual,  however,  its  absence 
does  not  exclude  cancer,  and  we  must  bear  in  mind  that  gall 
stones  with  cholangitis  may  raise  the  leucocyte  count  as  much  as 
cancer.     Simple  cysts  or  echinococcus  cysts  cause  no  leucocy- 
tosis, nor  does  syphilis  of  the  liver. 

6.  The  appearance  in  the  blood  of  large  numbers  of  eosino- 
philes,  myelocytes,  and  nucleated  corpuscles  during  the  course 
of  a  malignant  disease  points  to  a  bone  metastasis. 

7.  When  a  leucocytosis  which  has  disappeared  after  removal 


360  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

of  a  neoplasm  reappears,  we  may  expect  recurrence  of  the  growth 
shortly. 

8.  A  steadily  increasing  leucocytosis  in  a  case  of  malignant 
disease  points  to  a  rapidly  growing  tumor  or  to  the  occurrence 
of  metastasis. 

9.  Between  malignant  disease  and  pernicious  anaemia  the 
diagnosis  rests  on  the  following  points : 

I.  Color  index  low  in  malignant,  apt  to  be  high  in  per- 
nicious anaemia. 

II.  Leucocytes  often  increased  in  malignant,  diminished  in 
pernicious  anaemia. 

III.  Lymphocytes  often  decreased  in  malignant,  increased  in 
pernicious  anaemia. 

IV.  Average  size  of  red  cells  often  decreased  in  malignant, 
and  often  increased  in  pernicious  anaemia. 

Y.  If  nucleated  red  corpuscles  are  present  the  normoblasts 
are  in  a  majority  in  malignant  disease,  and  in  a  minority  in  per- 
nicious anaemia. 

10.  The  presence  of  leucocytosis  is  against  the  benignness  of 
any  tumor. 

11.  When  no  actual  increase  of  leucocytes  is  present,  an  in- 
creased  percentage   of  the  polymorphonuclear  variety  among 
those  present  may  have  the  same  significance  as  a  leucocytosis. 


CHAPTEE  XI. 

BLOOD  PARASITES  AND  INTESTINAL  PARASITES. 

EXAMINATION  FOR  THE  PLASMODIUM  MALARLE  AND  ITS  PRODUCTS. 

I.  Time  for  Examination.  — It  is  often  stated  that  the  organism 
is  most  easily  found  during  the  chill.     But  this  is  not  the  writer's 
experience.     During  a  chill  it  is  often  difficult  and  sometimes 
impossible  to  find  the  organisms.     Eight  hours  before  or  after 

a  chill  is  the  most  favorable  time  (Thayer),  although  parasites 
have  been  found  as  late  as  forty -eight  hours  after  the  last  chill. 
During  the  chill  many  organisms  retire  to  the  internal  organs. 

The  number  of  organisms  varies  a  great  deal.  In  some  cases 
they  are  present  in  every  field  of  a  one-twelfth  immersion  lens, 
while  in  others  we  may  find  only  one  after  an  hour  or  more  of 
patient  search.  In  the  majority  of  the  cases  occurring  near 
Boston,  it  needs  but  a  few  minutes'  search  to  find  them  if  the 
blood  be  taken  within  twelve  hours  before  or  after  a  chill,  and 
provided  no  quinine  has  been  lately  given.  Occasionally  in 
mild  cases  the  organisms  are  very  scanty ;  and  it  may  be  almost 
impossible  to  find  any.  The  quartan  and  sestivo-autumnal  forms 
of  malaria  are  so  rare  in  New  England  that  I  shall  not  attempt 
to  describe  in  detail  the  parasites  found  in  them,  but  shall  con- 
fine myself  mostly  to  the  parasites  of  common  tertian  and  double 
tertian  fevers  with  which  I  am  personally  familiar. 

II.  Method  of  Examination. — A  slide  of  fresh  blood  is  pre- 
pared as  above  described  (pages  6-8)  and  examined  with  a  one- 
twelfth  immersion  lens.1     Lower  powers  should  not  be  used, 
although  in  skilful  hands  they  are  often  sufficient.     Portions  of 
the  slide  in  which  the  corpuscles  do  not  overlie  each  other  should 
be  chosen  for  examination.     As  we  pass  the  slide  along  beneath 
the  lens  it  is  well  to  be  on  the  lookout  for  any  specially  large 
or  specially  pale  corpuscle.     Such  a  one  will  catch  the  eye  if  we 

1  In  cold  weather  both  slide  and  cover  should  be  warmed  before  using. 
Indeed  this  is  always  well,  as  it  makes  the  corpuscles  spread  better. 


362  SPECIAL  PATHOLOGY   OF  THE   BLOOD. 

are  on  the  watch  for  it,  even  though  the  slide  is  being  passed 
along  very  rapidly,  and  all  such  should  be  carefully  examined. 

Another  thing  to  watch  for  is  anything  black  or  dark  brown. 
If  the  slide  is  not  perfectly  clean,  or  if  the  cover-glass  has 
touched  the  skin  in  collecting  the  blood,  there  will  often  be  black 
spots  which  make  us  pull  up  short  and  examine,  only  to  find 
that  they  are  bits  of  dirt.  This  loses  time,  and  hence,  as  above 
noted,  the  importance  of  care  and  cleanliness  in  the  earlier  stages 
of  the  process. 

Besides  any  strikingly  pale  or  swollen  corpuscle  or  any  black 
dots,  we  should  be  on  the  lookout  for  any  movements  in  the 
field.  The  movements  of  Miiller's  "blood-dust"  (see  page  59) 
are  often  mistaken  by  beginners  for  those  of  the  malarial  organ- 
ism. Their  greatly  smaller  size  and  extracorpuscular  position 
serve  to  distinguish  them  in  most  cases.  I  have  sometimes 
thought  I  saw  pigment  in  these  bodies.  If,  as  Stokes  believes, 
the  "  blood-dust"  is  derived  from  the  leucocytes,  it  is  possible 
that  they  might  carry  out  with  them  some  pigment  ingested  by 
the  leucocyte. 

III.  The  Malarial  Organism. — (a)  "Hyaline  Forms."  In  the 
earlier  stages  of  its  growth,  i.e.,  during  and  soon  after  the  chill, 
the  organism  is  not  pigmented,  but  appears  only  as  a  light  spot 
in  the  pale  greenish-yellow  of  the  corpuscle.  It  practically  is 
never  to  be  seen  outside  the  corpuscle.  Most  malarial  organ- 
isms are  to  be  found  within  the  corpuscle,  and  only  there. l 

For  those  who  have  not  examined  many  specimens  of  ma- 
larial blood  it  is  a  very  difficult  thing  to  find  the  organism  at 
this  stage  of  its  growth,  and  the  number  of  mistakes  in  diag- 
nosis is  very  large.  I  always  look  with  great  suspicion  on  any 
report  of  malarial  blood  as  containing  only  "hyaline  forms." 

In  the  later  stages,  when  the  organism  has  become  well  pig- 
mented, there  is  nothing  that  at  all  resembles  it,  and  those  who 
have  seen  and  watched  it  a  few  times  can  hardly  mistake  any- 
thing else  for  it.  Not  so  with  the  so-called  "  hyaline"  or  young- 
est form  of  the  organism.  Personally  I  think  the  name  "  hyaline 
bodies"  is  responsible  for  a  part  of  the  mistakes.  We  are  led  to 
expect  something  more  shiny  and  refractile  than  the  organism 

1  Except  degenerate  forms,  free  flagellse,  and  spores  at  the  moment 
of  segmentation  (rarely  to  be  seen).  Crescents  and  ovoid  bodies  are  inter- 
cellular. 


BLOOD   PARASITES   AND   INTESTINAL   PARASITES.  363 

really  is,  and  so  are  misled  by  the  brilliant  white  circles  to  be 
found  at  the  centre  of  many  normal  corpuscles  under  certain 
conditions  of  light  and  partial  drying  up.  Time  and  again  I 
have  been  asked  to  look  at  malarial  organisms  (always  the 
"hyaline"  forms),  and  found  nothing  more  than  one  of  these 
effects  of  light  which  can  be  found  in  any  normal  blood,  if  the 
conditions  are  right.  There  are  certain  marks  by  which  we  can 
exclude  these  artifacts  from  consideration : 

I.  They  are  generally  far  too  numerous  to  be  malarial  or- 
ganisms.    One  usually  finds  a  dozen  or  more  in  a  field  which 
would  be  almost  unheard  of  with  the  plasmodium  malarise. 

II.  They  are  generally  in  the  centre  of  the  corpuscle,  while 
the  young  malarial  organism  is  almost  never  at  the  centre. 

III.  They  are  almost  invariably  round,  the  malarial  organism 
being  generally  more  irregular  and  branching. 

IV.  They  seem  to  increase  and  diminish  in  size  as  we  focus 
up  and  down  upon  them,  while  the  malarial  organism  only  grows 
dimmer  or  clearer. 

V.  They  are,  as  before  mentioned,  more  brilliantly  white  and 
shiny  than  the  malarial  organism,  which  has  often  a  faint  tinge 
of  yellow,  although  much  paler  than  the  surrounding  corpuscle 
substance. 

VI.  Their  edges  are  sharper,  the  malarial  organism  often 
fading  off  very  gradually  into  the  corpuscle  color. 

VII.  Their  movement  is  different.     The  malarial  organism 
is  not  at  all  the  only  thing  to  be  seen  moving  in  the  blood,  as 
has  sometimes  been  stated.     The  red  corpuscles  have  the  Brown- 
ian  motion,  and  as  they  begin  to  crenate  often  move  very  actively. 
But  their  motion  is  very  different  from  that  of  the  hyaline 
malarial  organism,  for  the  latter  changes  both  its  shape  and  its 
position  in  the  corpuscle  quite  rapidly,  while  the  motion  of  the 
light  space  in  an  ordinary  red  cell  is  a  wavy  undulation  of  the 
outlines  back  and  forth   without  any  considerable   change  of 
shape. 

(6)  As  soon  as  the  organism  gets  any  pigment  (and  there  are 
very  few  times  in  the  cycle  of  a  malarial  case  when  there  are  not 
some  pigmented  organisms  present),  the  active  rapid  motion  of 
the  black  pigment  dots  is  unlike  anything  else  seen  in  the  blood, 
and  when  once  recognized  can  never  be  forgotten  or  mistaken. 
It  is  only  when  the  pigment  has  ceased  moving  (owing  to  the 


364 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


death  of  the  organism)  that  the  differentiation  between  dirt  and 
malarial  pigment  becomes  difficult. 

Sometimes  it  is  really  difficult  to  distinguish  motionless  pig- 
ment in  a  malarial  organism  from  dirt  even  on  careful  scrutiny. 
The  best  way  is  to  get  a  fresh  slide  when  the  pigment  is  in 
motion. 

To  any  one  fairly  familiar  with  the  appearance  of  pigmented 
forms  of  malarial  organisms,  failure  to  find  them  in  a  case  of 
malaria  is  due  generally  (1)  to  too  thickly  spread  a  layer  of 

1  ^  34- 


10 


FIG.  37.— The  Parasite  of  Tertian  Malaria  (after  Thayer).     1,  Normal  red  cell ;  2  and  3, 
hyaline  parasites;  4,  5,  6,  7,  pigmented  forms;  8,  9,  10,  11,  segmentation. 

blood,  the  corpuscles  overlying  each  other;  (2)  to  not  looking 
long  enough  (Figs.  37  and  38) ;   (3)  to  lack  of  proper  light. 

I  have  not  attempted  to  go  into  the  marks  by  which  we  can 
differentiate  the  tertian,  quartan,  and  eestivo-autumnal  forms  of 
the  organism — for  clinical  evidence  usually  suffices  to  determine 
this  point.  For  information  on  this  and  all  the  finer  points  in 
regard  to  the  life  history  and  habits  of  the  organism  W.  S. 
Thayer 's  admirable  monograph  should  be  consulted.  Here  it 
is  sufficient  to  say  that  as  the  paroxysm  draws  near,  the  pig- 
ment granules  begin  to  work  in  toward  the  centre  in  radiating 
lines  until  they  are  all  collected  in  a  solid  black  mass.  While 
this  is  going  on,  the  pigment  granules  not  infrequently  gather 
into  short  rod-like  masses  not  at  all  unlike  bacilli. 


BLOOD   PARASITES  AND   INTESTINAL  PARASITES. 


365 


Round  the  central  mass  of  pigment,  indistinct  radiating 
divisions  may  sometimes  be  seen  just  before  the  organism  breaks 
up.  These  divisions  have  been  compared  to  the  petals  of  a 
flower,  but  it  is  very  difficult  to  see  more  than  the  faintest  indi- 


©    ©     © 


10 


13 


15* 


11 


FIG.  38.— Parasite  of  Quartan  Malaria  (after  Thayer).    1,  Normal  red  cell;  2,  hyaline 
parasite;  3  to  11,  pigmented  forms;  13  to  15,  segmenting  forms. 


o  j  © 


11 


14 


© 


13 


FIG.  39.— Parasite  of  JEstivo-Autumnal  Malaria  (after  Thayer).     1  to  6,  Young  forms; 
7  to  13,  mature  forms;  14  to  16,  segmenting  forms. 


•366  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

cations  of  such  an  arrangement  in  most  specimens.  The  cor- 
puscle itself  is  by  this  time  wholly  lost  to  sight. 

(c)  The  next  stage,  that  of  segmentation,  is  less  commonly 
seen  than  those  just  mentioned,  and  is  only  to  be  satisfactorily 
observed  by  using  a  warm  stage  (vide  supra,  page  8)  and  spend- 
ing considerable  time  on  the  watch  for  it.  Around  the  central 
pigment  mass  we  may  sometimes  see  in  ordinary  specimens 
(without  warm  stage)  the  faint  outlines  of  a  group  of  small 
•spherical,  colorless  bodies  (vide  Fig.  2,  9,  Plate  I.)  which  are 
the  new  generation  of  young  organisms. 

Now  we  should  expect  that  with  the  next  step  in  the  process 
we  should  find  these  young  plasmodia  free  in  the  plasma  or  en- 
tering a  fresh  set  of  red  corpuscles.  But  in  the  peripheral  cir- 
culation this  is  rarely  if  ever  observed.  Thayer  in  his  immense 
experience  has  never  seen  them.  The  next  evidence  we  have  of 
the  organism  is  as  a  "hyaline"  body  inside  the  corpuscle  again. 

Almost  all  stages  of  the  growth  of  the  plasm  odium  which 
we  can  watch  in  the  blood  drawn  from  the  peripheral  circulation 
take  place  within  the  corpuscle.  It  is  true  that  as  the  pigrnented 
organism  gets  towards  its  full  growth,  and  before  the  granules 
have  begun  to  gather  at  the  centre,  we  may  find  it  very  difficult 
to  find  any  trace  of  corpuscle  substance  around  the  margin  of 
the  plasmodium.  Sometimes  we  see  a  ring  of  non-pigmented 
glistening  white  substance  outside  the  moving  black  dots  (see 


FIG.  40.— Flagellate  Malarial  Organisms  (after  Thayer). 

Fig.  2,  7,  Plate  I.)  standing  out  light  against  the  darker  plas- 
ma. This  I  suppose  to  be  the  remains  of  the  corpuscle.  It 
Is  not  described  or  pictured  in  the  standard  works  on  the  sub- 
ject. 

Occasionally  we  do  find  pigmented  bodies  wholly  outside 
the  corpuscle,  either  partly  or  fully  grown.     In  the  intracorpus- 


BLOOD   PARASITES   AND   INTESTINAL   PARASITES.  367 

cular  forms  the  distinction  between  plasmodium  and  corpuscle 
substance  is  not,  I  think,  so  sharp  and  clear  as  one  would  be  led 
to  expect  from  the  plates  in 
standard  works.  With  aver- 
age eyes  and  lenses  the  out- 
line of  the  organism,  as 
distinguished  both  from  its 
pigment  granules  and  the 
surrounding  corpuscles,  is 
not  easy  to  see.  It  is  the 
moving  pigment  granules  that 
attract  our  notice. 

(d)  It  remains  to  speak  of 
three  comparatively  small 
points : 

1.  The    presence    of    fla- 
gella. 

2.  Pigmented  leucocytes. 

3.  Crescents  and  o voids. 
1.  Toward  the  end  of  the 

life  history  of  a  malarial  par- 
asite, it  sometimes  makes  its 
presence  very  obvious  in  the 
microscopic  field  by  knock- 
ing about  the  surrounding 
corpuscles  with  its  arms  or 
"flagetta."  Exactly  why  and 
under  what  conditions  it 
shows  or  fails  to  show  these 
appendages  is  not  known.1 
They  are  about  two  or  three 
times  as  long  as  a  red  cor- 
puscle and  one-sixth  or  one- 
eighth  as  wide.  They  are 
usually  to  be  inferred  rather 
than  directly  seen,  as  they 
are  nearly  transparent.  Our 

1  McCallum  has  recently  offered 
interesting  evidence  that  they 
are  sexual  organs.  FlG"  41-Flasellate  Malarial  Organisms. 

(After  Manson's  photographs.) 


368  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

attention  is  attracted  by  an  active  motion  among  a  group  of  red 
cells  apparently  of  spontaneous  origin.  Gradually  we  make  out 
a  filmy  whip-like  tail  attached  to  an  adjacent  malarial  parasite. 
Sometimes  there  is  pigment  dotted  along  the  flagellum  itself, 
and  then  we  can  make  it  out  more  easily.  Its  distal  end  is 
especially  apt  to  be  pigmented,  and  by  the  help  of  this  pig- 
ment we  make  out  that  it  is  bulbous,  while  similar  swell- 
ings can  sometimes  be  seen  at  other  points  along  the  flagel- 
lum (see  Fig.  41).  Such  a  flagellum  may  break  off  and  dart 
about  free  among  the  corpuscles.  As  the  pigmented  end  is 
sometimes  all  that  we  can  see  of  it,  this  gives  rise  to  the  appear- 
ance of  a  very  small,  actively  locomotive  pigmented  body  free 
among  the  corpuscles,  and  its  course  may  be  followed  through 
several  fields. 

When  the  flagella  have  ceased  moving,  their  presence  is  gen- 
erally detected,  if  at  all,  by  an  irregular  line  of  pigment  dots 
about  20 1*,  long,  which  will  be  shown  by  careful  focussing  to  be 
contained  within  a  nearly  transparent  membrane. 

Very  often  we  find  a  leucocyte  in  process  of  closing  round 
the  flagellated  parasite.  Manson  has  lately  succeeded  in  stain- 
ing the  flagellae,  and  the  accompanying  photographs  are  from 
his  stained  specimens. 

2.  Pigmented  leucocytes,   containing  the  whole  or  part  of 
malarial  organisms  or  simply  blocks  or  granules  of  black  pig- 
ment, are  usually  to  be  found  in  the  blood  near  the  time  of  the 
chill.     The  pigment  is  to  be  carefully  distinguished  from  the 
granules  present  in  most  leucocytes,  which  in  certain  lights  look 
quite  dark  even  if  unstained,  dark  enough  to  be  mistaken  for  pig- 
ment by  the  untrained  eye.     Careful  focussing  and  changing  the 
light  will  easily  determine  which  we  are  dealing  with,  provided 
we  are  familiar  with  the  appearances  of  leucocytes  in  the  fresh 
unstained  blood.     In  certain  forms  of  the  disease  in  which  the  or- 
ganisms themselves  retire  to  the  internal  organs,  the  presence  of 
pigmented  leucocytes  may  be  the  only  evidence  of  the  disease  to 
be  found  in  the  peripheral  blood  and  is  therefore  of  the  greatest 
importance. 

3.  Crescentic   forms  are  not  often  seen  in  New  England. 
They  are  found  only  in  the  sestivo-autumnal  forms  of  malaria 
which  occur  chiefly  in  the  South  and  West  and  have  been  seldom 
reported  in  any  Northeastern  State  except  in  patients  who  have 


BLOOD   PARASITES   AND    INTESTINAL   PARASITES.  369 

brought  them  from  the  South  and  West.  I  have  never  seen  these 
crescentic  forms  except  in  the  stained  specimens  of  other  obser- 
vers, and  my  ideas  of  them  are  mostly  second-hand  (Fig.  42). 
Full  account  of  them  will  be  found  in  the  monograph  of 
Thayer's  above  referred  to. 

Hitherto  I  have  spoken  wholly  of  the  appearance  of  the  par- 


asites in  the  fresh  unstained  blood,  this  being  by  far  the  simplest, 
easiest,  and  surest  way  of  finding  them  and  the  only  way  of 
studying  their  development.  In  cases  in  which  we  cannot  make  a 
microscopic  examination  at  the  bedside,  we  can  sometimes  pre- 
serve the  organism  alive  between  slide  and  cover-glass,  until 
we  can  get  it  to  the  nearest  microscope,  even  if  this  takes  sev- 
eral hours.  I  have  carried  specimens  in  my  handbag  a  whole 
morning  and  yet  found  the  pigment  of  the  malarial  parasite  in 
motion  at  the  end  of  that  time.  Warm  weather  favors  this. 
When  it  is  necessary  to  keep  the  specimen  some  time  before 
examination,  it  is  best  to  paint  on  the  slide  a  ring  of  vaseline  or 
any  gummy  substance,  and  allow  the  drop  of  blood  to  spread  out 
inside  this  ring  so  that  the  margins  of  cover  glass  are  glued  to 
the  slide  by  the  oily  substance  and  the  entrance  of  air  is  pre- 
vented. The  cedar  oil  ordinarily  used  for  immersion  lenses 
answers  the  purpose  very  well.  Both  slide  and  cover  should  be 
gently  warmed  before  spreading  the  drop  of  blood. 

Many  physicians  who  cannot  possibly  carry  a  microscope 
about  with  them  can  easily  find  room  for  a  few  slides  and  cover- 
glasses  and  they  may  be  of  great  service. 

When  specimens  have  to  be  sent  by  mail,  or  for  long  dis- 
tances, or  in  cold  weather  we  have  to  fall  back  on  dried  speci- 
mens prepared  as  described  on  page  43,  provided  always  that  a 
24 


870  SPECIAL    PATHOLOGY    OF    THE    BLOOD. 

bedside  examination  is  impossible.     These  can  be  stained  by 
one  of  the  following  methods : 

Leave  the  specimen  for  half  an  hour  or  more  in  equal  parts 
of  ether  and  absolute  alcohol,  dry  them  in  the  air,  stain  for 
from  one-half  to  five  minutes  in  a  one-half-per-cent  solution  of 
eosin  in  sixty-per-cent  alcohol,  wash  in  water,  dry  and  stain 
one -half  to  one  minute  in  concentrated  watery  solution  of 
methylene  blue ;  wash  again  in  water,  dry  in  filter  paper,  and 
mount  in  Canada  balsam. 

Personally  I  have  found  this  method  rather  unsatisfactory  on 
account  of  the  different  intensity  of  different  eosin  stains  and 
the  consequent  need  of  finding  out  by  experiment  how  long 
(within  the  limits  of  one-half  to  five  minutes)  the  specimen  is  to 
be  stained  before  a  distinct  yet  not  violent  red  color  is  at- 
tained in  the  protoplasm  of  the  corpuscles.  The  blue  stains 
the  plasmodium  itself  in  contrast  with  the  pink  corpuscle 
substance  around  it;  the  pigment  granules  remain,  as  in 
the  fresh  specimen,  black  or  brownish  black.  (See  Fig.  3, 
Plate  I.) 

Some  find  the  stain  of  Plehn  simpler  and  more  satisfactory 
as  well  as  quicker.  By  this  method  we  leave  the  specimens 
only  three  or  four  minutes  in  absolute  alcohol  and  then  stain  five 
or  six  minutes  in  the  following  mixture : 

Concentrated  watery  solution  methylene  blue 60 

One-half-per-cent  solution  of  eosin  in  seventy-five-per-cent 

alcohol 20 

Distilled  water 40 

Twenty  per  cent  NaOH 12  gtt. 

Wash  in  water  and  mount  in  Canada  balsam. 

The  trouble  of  double  staining  and  the  uncertainty  as  to  the 
length  of  time  are  avoided  by  this  solution,  and  the  parasites 
are  sometimes  beautifully  stained.  Yet  on  the  whole  I  have 
had  better  success  with  the  eosin  and  methylene  blue  de- 
spite its  difficulties.  The  ordinary  Ehrlich-Biondi  mixture 
may  also  be  used  to  demonstrate  pigmented  forms.  The  organ- 
ism itself  does  not  stain  at  all  with  this  mixture  but  stands  out 
light  against  the  yellow  of  the  corpuscle,  the  pigment  looking 
as  it  does  in  the  live  parasite.  The  hyaline  forms  need  some 
other  stain  for  satisfactory  recognition,  but  it  is  sometimes  con- 


BLOOD   PARASITES   AND   INTESTINAL   PARASITES.          371 


FIG.  43. 


venient  to  use  the  same  stain  for  the  differential  count  and  the 
malarial  organism,  as  for  instance  when  we  have  only  one 
cover-glass  preparation  in  a  case  of 
doubtful  diagnosis.  Fixing  the 
specimen  in  alcohol  and  ether  is 
here  far  better  than  heat;  other- 
wise the  technique  is  as  above 
described  under  Triple  Staining 
(page  44).  The  general  appear- 
ance of  the  organism  so  stained  is 
shown  in  Fig.  43. 

If  the  organisms  are  fairly  num- 
erous and  the  technique  is  good 
we  can  find  them  by  this  method 
even  in  preparations  months  old. 
In  general,  however,  it  is  very  in- 
ferior to  the  examination  of  the  live 
organism  in  the  fresh  blood,  and 
gives  many  more  chances  for  error. 

So  much  for  technique. 

We  often  hear  reports  of  fruitless  search  for  the  parasite  in 
the  blood  of  malarial  patients,  but  the  regularity  with  which 
they  are  found  at  all  the  larger  hospitals  and  by  all  practised 
observers  in  this  and  other  countries  leaves  no  doubt  that  they 
are  to  be  found  in  every  case  during  some  portion  of  the  cycle. 
The  practice  of  taking  blood  during  a  chill  contributes,  I  believe, 
to  the  number  of  unsuccessful  endeavors  to  find  the  organism ; 
as  mentioned  above,  this  is  the  worst,  not  the  best  time  to  look 
for  them.  Too  thick  a  layer  of  blood  between  slide  and  cover 
accounts  for  some  failures,  as  I  have  found  in  personal  experi- 
ence. 

No  doubt,  in  many  cases  in  which  we  fail  to  find  the  organ- 
ism in  supposed  malaria  a  faulty  diagnosis  is  the  reason.  Many 
of  the  cases  in  which  latent  malaria  is  supposed  to  have  "  come 
out"  after  a  surgical  operation  are  exploded  by  the  negative 
examination  for  parasites  and  the  positive  indications  of  pus- 
pocketing  which  are  afforded  by  a  marked  leucocytosis  (never 
present  in  simple  malaria),  and  the  fact  of  insufficient  wound 
drainage  is  often  disclosed  in  this  way.  Whenever  we  see  the 
leucocytes  increased  we  begin  to  doubt  the  existence  of  an  un- 


372  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

complicated  malaria ;  if,  furthermore,  we  see  no  signs  of  any  pal- 
lor of  the  corpuscles  we  doubt  the  presence  of  malaria  still  more, 
as  there  is  no  more  rapid  deglobularizer  than  the  malarial  or- 
ganism. 

How  long  after  a  chill  the  organisms  may  still  be  found  in  the 
peripheral  blood  is  difficult  to  decide,  but  certainly  they  can  be 
found  any  time  within  twenty-four  hours  after  the  last  chill, 
unless  quinine  has  been  given,  and  sometimes  even  if  it  has  been 
given. 

OTHER  CHANGES  IN  THE  BLOOD. 

Red  Corpuscles. — The  following  is  from  Thayer's  remarkable 
monograph : 

"  A  reduction  in  red  corpuscles  follows  each  paroxysm ;  these 
reductions  are  more  marked  after  the  early  paroxysms  than  after 
those  occurring  later.  When  a  certain  degree  of  anaemia  has 
been  reached  the  losses  per  paroxysm  are  much  less.  When 
the  number  of  corpuscles  is  reduced  to  2,000,000  or  1,000,000 
there  is  little  tendency  toward  a  further  fall ;  sometimes  there 
may  be  slight  rises  in  the  curve  between  the  paroxysms ;  often, 
however,  the  number  of  corpuscles  remains  stationary  for 
weeks. 

"  In  pernicious  cases  the  number  of  corpuscles  may  fall  be- 
tween paroxj^sms."  Kelsch  has  seen  the  count  decrease  to  as 
small  a  number  as  500,000  per  cubic  millimetre.  The  diminu- 
tion is  greater  the  longer  the  disease  lasts  and  the  more  in 
tense  its  manifestations. 

During  the  paroxysms,  particularly  the  earlier  ones,  the  red 
cells  tend  to  increase  in  number. 

In  tertian  and  quartan  fevers  there  is  a  rapid  and  almost 
complete  restitution  of  the  corpuscles  during  the  afebrile 
period. 

In  sestivo-autumnal  fevers  the  number  of  red  cells  bears  a 
direct  relation  to  the  number  of  organisms.  Crescentic  bodies 
seem  to  have  no  influence  on  the  number  of  red  cells. 

When  after  a  paroxysm  the  number  of  corpuscles  has  been 
greatly  diminished  the  succeeding  paroxysm  may  be  followed  by 
a  slight  reduction  only  or  even  by  an  increase. 

Bignami  and  Dionisi  distinguish  three  types  of  post-malarial 
anaemia : 


BLOOD    PARASITES    AND    INTESTINAL   PARASITES.  373 

1.  Ordinary  secondary  anaemia,  but  with  leucopenia  instead 
of  leucocy tosis ;  such  cases  usually  recover. 

2.  Anaemia   practically  identical   with  pernicious  anaemia, 
megaloblasts  being  present,  and  ending  fatally. 

3.  Anaemias  which  are  progressive,  because  the  bone  marrow 
cannot  compensate  for  the  losses  of  corpuscles. 

The  rapidity  of  the  diminution  in  red  cells  may  be  very  great. 
Kelsch's  count  of  500,000  cells  per  cubic  millimetre,  mentioned 
above,  was  after  thirty  days'  illness.  Grawitz  has  seen  a  loss  of 
4,000,000  cells  in  six  days. 

Qualitative  changes  are  those  of  severe  secondary  anaemia, 
deformities  in  size  and  shape,  normoblasts,  occasional  megalo- 
blasts in  the  worst  cases,  motility  in  the  "  pale,  ghostly"  cells. 

Haemoglobin. — The  loss  of  haemoglobin  bears  usually  a  direct 
relation  to  the  number  of  parasites  in  the  blood.  As  a  rule,  the 
corpuscles  and  haemoglobin  are  diminished  proportionally  (color 
index  =1)  but  sometimes  the  haemoglobin  is  reduced  dispro- 
portionately. 

In  convalescence  the  restitution  of  haemoglobin  is  often  in- 
complete; persons  living  in  malarial  districts  have  often  a 
slightly  smaller  percentage  of  haemoglobin  than  those  living 
elsewhere. 

The  rapid  diminution  in  haemoglobin  is  a  valuable  point  in 
differential  diagnosis  between  malaria  and  typhoid  or  pneu- 
monia. 

White  Cells. — The  number  of  leucocytes  is  usually  subnor- 
mal, but  show  a  slight  increase  at  the  beginning  of  the  par- 
oxysm. Following  this  increase  there  is  a  rapid  decrease  con- 
tinuing throughout  the  paroxysm. .  The  small  number  of 
leucocytes  is  to  be  seen  at  the  end  of  the  paroxysm  when  the 
temperature  is  subnormal.  From  this  time  it  shows  a  gradual 
increase  until  the  beginning  of  the  next  attack  (Billings) . 

In  a  general  way  the  white  cells  follow  the  same  course  as  do 
the  red. 

The  differential  count  shows  a  lymphocytosis  whenever  the 
white  cells  are  subnormal,  the  larger  forms  of  lymphocytes  being 
especially  numerous,  while  the  polymorphonuclear  cells  and 
eosinophiles  are  scanty. 

In  four  cases  of  post-makrial  anaemia  Billings  found  quite 
marked  leucocy  tosis. 


374 


SPECIAL   PATHOLOGY    OF   THE    BLOOD. 


The  occurrence  of  pigmented  leucocytes  has  already  been 
mentioned. 

Grawitz  and  others  have  noticed  an  increase  of  eosinophiles 
in  post-malarial  anaemia.  I  have  frequently  found  small  per- 
centages of  myelocytes,  three  per  cent  being  the  highest  in  my 
experience. 

MALARIAL  H^EMOGLOBIN^EMIA. 

During  the  paroxysms  of  this  form  of  the  disease,  the  num- 
ber of  the  red  cells  is  much  diminished,  rouleaux  not  formed, 
marked  poikilocytosis  with  nucleated  forms.  The  leucocytes 
are  increased.  The  regeneration  is  very  swift,  twenty-four  to 
forty -eight  hours  being  usually  sufficient  to  re-establish  normal 
conditions. 


FILARIA  SANGUINIS  HOMINIS. 

Although  most  commonly  found  in  tropical  countries,  one 
species  of  this  worm  is  not  very  uncommonly  found  in  various 
parts  of  the  United  States.  Any  case  of  chylous  urine  or  ele- 
phantiasis should  lead  us  to  make  a  careful  examination  of  the 
blood  for  the  filaria.  There  are  at  least  four  species  of  filaria, 
one  of  which  is  present  in  the  blood  chiefly  at  night,  another 
chiefly  during  the  daytime,  and  another  continuously.  Only  the 
filaria  nocturna  has  thus  far  been  seen  in  America  (Fig.  44). 

In  examining  for  the  filaria  a  slide  of  the  fresh  blood  is  pre- 


FIG.  44.— The  Filaria  Sanguinis  Hominis.  The  head,  curled  up,  is  seen  at  the  right  of  the 
cut,  the  tail  at  the  left.  Instantaneous  photomicrograph.  Four  hundred  diameters 
magnification. 

pared  in  the  usual  way,  but  after  8:30  o'clock  in  the  evening,1  and 
examined  at  once.  The  embryo  of  this  parasite  (which  is  what 
1  In  persons  who  sleep  in  the  daytime  and  work  at  night  the  habits  of 
the  filaria  are  said  to  become  reversed,  so  that  it  appears  in  the  peripheral 
circulation  chiefly  in  the  daytime,  and  is  to  be  looked  for  then. 


FILARIA   SANGUINIS   HOMINIS.  375 

we  find  in  the  human  blood)  is  from  one-ninetieth  to  one  seven- 
tieth of  an  inch  in  length,  i.e.,  about  fifty  times  the  diameter  of 
a  red  cell,  and  about  the  width  of  a  red  corpuscle.  Seen  in  the 
blood  it  retains  its  vitality  and  motile  power  for  a  considerable 
time,  so  that  its  motions  may  continue  a  week  or  more  between 
slide  and  cover-glass.  Cold  has  little  effect  upon  it,  even  freez- 
ing temperature  failing  to  do  more  than  make  the  movements 
slower. 

A  distinction  can  generally  be  made  out  between  the  embryo 
proper  and  its  sheath  (see  Fig.  45).  From  this  sheath  the 
embryo  escapes  when  in  the  blood  of  the  mosquito,  which  insect 


FIG.  45.— Tail  of  Filaria,  showing  prolongation  of  the  sheath  beyond  the  end  of  the  embryo 
itself.     Magnified  800  diameters. 

acts  not  infrequently  as  intermediary  host  and  conveys  the  para- 
site indirectly  from  man  to  man  through  the  medium  of  water. 
After  sucking  in  the  organism  with  the  blood  the  mosquito  lays 
its  eggs  and  dies  in  some  neighboring  pond  or  stream  whence  the 
filaria  again  gains  access  to  men. 

It  is  a  long,  slender,  snake-like,  gracefully  shaped  worm,  and 
when  alive  its  activity  is  so  great  that  measurements  and  obser- 
vations of  its  structure  cannot  be  made  till  it  is  paralyzed  by 
approaching  death  (Fig.  46). 


376  SPECIAL   PATHOLOGY   OP   THE   BLOOD. 

Posteriorly  it  tapers  for  one-fifth  its  length  down  to  a  very 
sharp  point.     The  extreme  end  of  the  tail  often  looks  as  if  ar- 


FIG.  46.— The  Movement  of  a  Single  Filaria  during  Four  Successive  Exposures  of  one-fifth 
of  a  second  each,  the  entire  series  occupying  less  than  five  seconds.  Magnified  800 
diameters. 

ticulated,  for  it  does  not  harmonize  with  the  general  curve  of 
the  body,  but  lies  bent  at  an  angle.  Toward  the  head  it  tapers 
very  slightly  and  when  alive  a  "  pouting"  movement  as  if  of  breath- 
ing can  be  seen  at  its  very  extremity.  About  the  middle  of  the 
body  a  granular  aggregation  can  be  made  out  along  the  central 
axis  of  the  animal.  Except  for  this  granular  portion  the  para- 
site is  so  translucent  that  it  is  not  easy  to  make  it  out  at  first. 
The  distinction  of  body  and  sheath  mentioned  above,  appears 
as  a  "clear  space"  at  each  end  of  the  body  (vide  Fig.  45). 
After  the  motions  have  ceased  it  becomes  darker  and  traces  of 
transverse  striation  may  be  seen  (Fig.  47). 

It  has  no  locomotive  power  and  confines  itself  to  wriggling  in 
the  same  spot.  Saussure1  says  he  has  watched  them  "fighting 
with  each  other  for  hours." 

The  head  of  the  filaria  is  said  by  some  authorities  to  be  sup- 

1  Philadelphia  Medical  News,  June  28th,  1890,  where  he  reports  twenty 
cases  seen  in  Charleston,  S.  C. 


FILARIA    SANGUINIS   HOMINIS. 


377 


FIG.  47. — Head  of  Filaria.    Shows  structure  and  beginning  granular  degeneration.     Magni- 
fied 1,500  diameters. 


FIG.  48.— Head  of  Filaria  Magnified  1,500  Diameters.     The  blur  in  front  of  the  head  may  be 
due  to  the  motion  of  flagella. 


378  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

plied  with  feelers  or  flagella,  and  Manson  describes  what  he  calls 
a  "cephalic  armature"  or  fang  (Fig.  48). 

The  same  organism  can  sometimes  be  found  in  the  chylous 
urine,  but  not  every  case  of  chyluria  is  due  to  the  filaria  san- 
guinis  hominis.  In  a  considerable  proportion  of  cases  no  such 
organism  is  to  be  found. 

Henry  (Med.  News,  May  2d,  1896)  succeeded  in  staining  the 
parasites  intra  vitam  by  giving  the  patient  considerable  doses 
of  methylene  blue  internally  for  some  weeks.  Only  a  faint 


FIG.  49.— Head  of  Filaria  Overlapping  a  Red  Corpuscle.    The  appearance  might  be  mis- 
taken for  the  cephalic  end  of  a  sheath. 

bluish  tinge  was  imparted,  however,  to  the  organism  by  this 
method. 

For  finding  the  parasite  it  is  best  to  use  a  low  power,  not  an 
immersion  lens,  and  the  whole  of  several  slides  should  be  looked 
over. 

Specimens  can  be  dried  and  preserved  for  staining  provided 
we  do  not  heat  them  over  a  lamp  or  pass  them  through  a  flame. 
Manson1  stains  with  eosin  and  mounts  in  "  glvcerin  jellv"  (Fig. 
49). 

Several  other  species  have  been  observed  in  England  in 
negroes  from  the  Congo  River,  but  not  hitherto  in  America. 
But  as  it  frequently  is  to  be  found  in  persons  who  have  no 
symptoms  whatever,  it  may  well  be  that  some  of  these  other 
species  would  be  found  here  if  one  took  the  trouble  to  seek  out 
natives  of  Southern  China  (one  out  of  every  ten  of  whom  carries 

1  The  *  Filaria  Sanguinis  Hominis,"  by  Patrick  Manson,  M.D.,  Amoy, 
China,  1883. 


SPIROCH^TE   OF   RELAPSING  FEVER. 


379 


about  the  filaria  in  his  blood),  or  of  Central  Africa,  or  other 
tropical  regions. 

SPIROCH^ETE  OF  RELAPSING  FEVER. 

During  the  febrile  paroxysms  of  relapsing  fever,   and   for 
one  or  two  days  before  them,  Obermeyer  and  others  have  found 


FIG.  50.— Spirochaetes  of  Relapsing  Fever  in  Human  Blood. 


FIG.  51.— Spirochsetes  of  Relapsing  Fever  in  Human  Blood. 


380  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


JJ^i: 

ipv^ 


FIG.  53. 
Spirochaetes  of  Relapsing  Fever. 


SPIROCH^ETE    OF   RELAPSING   FEVER. 


381 


\ 


constantly  present  in  the  peripheral  circulation  a  parasite  whose 

length  averages  about  six  times  the  diameter  of  a  red  corpuscle. 

Even  under  high-power  lenses  it  is 

a  mere  thread  in  width,  curled  upon 

itself  like  a  corkscrew  and  actively  \ 

motile,    so   that   in    examining   the 

blood  with  a  low  power  we  get  "  a 

peculiar  impression  of  disturbance" 

among  the  red  cells. 

The  number  of  twists  in  this 
spiral-shaped  organism  varies  a 
good  deal,  and  one  of  its  motions 
consists  in  contracting  and  extend- 
ing itself  like  a  spiral  spring.  It 
can  thus  multiply  its  own  length 
three  or  four  times.  It  has  also  a 
delicate,  wavy,  but  rapid  motion 
along  its  long  axis.  The  whole 
thread,  or  a  part  of  it  only,  may 
have  these  motions.  Further,  the 
whole  parasite  has  power  of  loco- 
motion apparently  independent  of 
the  currents  in  the  blood  plasma  of 
a  slide  and  cover-glass  specimen. 
Its  locomotion  is  slow  compared  to 
the  movements  above  described. 
Particularly  in  the  blood  post  mor- 
tem they  are  apt  to  wind  themselves 
into  each  other  so  as  to  seem  much 
larger  than  they  actually  are,  and 
sometimes  a  large  "nest"  of  them 
may  look  like  a  leucocyte,  except 
for  the  fine  wavy  threads  which  can 
be  seen  in  motion  at  the  periphery 
of  the  mass. 

The  number  present  in  the  blood 

is  very  much  smaller  at  the  beginning  of  a  paroxysm  than  after 
the  second  day.  During  the  first  few  hours  of  a  febrile  period 
Mocyntkowsky  could  find  only  one  spirochsete  in  ten  or  twenty 
microscopic  fields,  while  later  on  he  saw  twenty  or  thirty  of 


FIG.  54.— Leucocytes  Containing 
Spirochaetes. 


382  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

them  in  a  single  field.  There  are  usually  more  parasites  with 
each  successive  paroxysm. 

Blood  taken  from  different  parts  of  the  body  often  shows  a 
great  difference  in  the  number  of  organisms  to  be  found.  The 
life  history  of  a  single  parasite  seems  to  be  very  short,  but  they 
multiply  with  the  greatest  rapidity.  Albrecht  has  seen  them  so 
increase  within  six  hours  that  whereas  at  first  he  saw  only  a 
few  in  the  whole  slide  he  later  found  many  in  each  field.  As 
the  spirochsete  dies,  its  movements  get  languid  and  finally  it 
breaks  up  into  small  granular  bits  (spores?). 

Between  paroxysms  the  spirochsetes  are  not  found,  but  there 
are  to  be  seen  peculiar  highly  refractile  globules  compared  by 
v.  Jaksch  to  a  diplococcus.  The  latter  author  believes  that  he 
has  seen  these  develop  into  the  spirochsete  at  the  beginning  of 
a  paroxysm  and  hence  believes  them  to  be  spores. 

This  spirochaete  is  found  in  all  cases  of  relapsing  fever  and 
in  no  other  known  disease,  so  that  like  the  plasmodium  malariae 
it  is  pathognomonic  and  of  the  highest  importance. 

Ansemia  and  leucocytosis  (during  the  paroxysm)  are  among 
the  secondary  results  of  the  presence  of  this  parasite  in  the 
blood. 

A  certain  resemblance  has  been  noted  between  the  spirochsete 
and  a  free  flagellum  broken  off  from  a  malarial  parasite,  but  the 
clinical  history  and  the  presence  or  absence  of  other  evidence  of 
malaria  in  the  blood  would  easily  decide  the  question  of  diag- 
nosis. 

Technique  of  Examination.—  As  in  looking  for  the  malarial 
organism  it  is  best  to  examine  the  blood  fresh  between  a  slide 
and  cover-glass  (vide  supra,  page  7)  and  to  use  an  oil  immer- 
sion lens.  In  dried  specimens  the  organism  can  be  stained 
with  fuchsin,  but  it  is  much  more  difficult  to  recognize  than  in 
the  fresh  blood.  Phagocytosis  (see  Fig.  54)  can  easily  be 
watched  in  the  peripheral  blood. 

DISTOMUM    H^MATOBIUM. 

Bilharz  found  this  parasite  post  mortem  in  the  large  internal 
veins  (portal,  splenic,  mesenteric,  etc. ),  but  as  it  has  never  been 
seen  in  the  peripheral  circulation  its  clinical  importance  is  thus 
far  nil. 


ANAEMIA    DUE    TO   INTESTINAL   PARASITES.  383 


BACTERIA  IN  THE  BLOOD. 

(a)  Cover-Glass  Specimens. — Bacilli  of  anthrax,  tuberculosis, 
glanders,  grippe,  typhoid  fever,  and  tetanus  have  been  demon- 
strated in  the  blood  of  human  beings  as  well  as  have  the  pyo- 
genic  streptococci  and  staphylococci,  the  diplococcus  lanceolatus, 
the  gonococcus,  and  the  bacillus  coli  communis.     Nevertheless  it 
is  exceedingly  difficult  and  frequently  impossible  to  find  them, 
and  no  considerable  practical  use  has  as  yet  been  made  of  the 
-cover-slip  examination  of  blood  for  micro-organisms. 

Gunther's  method  is  an  excellent  one.  Cover-glass  speci- 
mens of  the  blood  are  prepared  as  above  described  (page  43), 
and  left  a  few  seconds  in  five-per-cent  acetic  acid  to  render  the 
red  cells  invisible ;  the  acetic  acid  is  then  shaken  (not  tvashed)  off 
and  the  cover-glass  held  over  the  mouth  of  a  bottle  of  strong 
ammonia  water  to  neutralize  the  remaining  acid.  The  covers 
are  then  stained  with  the  Ehrlich-Weigert  solution,1  mounted  in 
balsam,  and  examined  with  a  one-twelfth  immersion  lens. 

(b)  Cultures  (see  above,  page  47). 

.    ANAEMIA   DUE  TO  INTESTINAL  PARASITES. 

The  bothriocephalus  latus,  ankylostoma  duodenale,  and  a 
few  other  parasites  are  capable  of  producing  by  their  presence 
in  the  intestine  a  very  severe  anaemia,  which  may  be  indistin- 
guishable from  pernicious  anaemia.  As  yet  no  such  case  has 
been  reported  in  this  country,  but  Askanazy2  and  Schaumann3 
have  carefully  studied  the  disease  in  Germany  and  found  that 
the  blood  may  correspond  exactly  with  that  of  pernicious  anae- 
mia, including  the  presence  of  high  color  index  and  of  a  major- 
ity of  megaloblasts  among  the  nucleated  red  cells  present.  Yet 
such  cases  may  be  rapidly  and  permanently  cured  by  expelling 
the  parasites  from  the  intestine.  No  special  description  of  the 
blood  states  need  be  given,  as  they  present  nothing  which  has 

1  To  6  c.c.  of  distilled  water  add  ten  drops  of  aniline  oil  and  filter.    To 
the  nitrate  add  a  saturated  alcoholic  solution  of  gentian  violet  till  slight 
(transient)  turbidity  appears.     On  the  surface  of  this  solution  in  a  watch 
glass  float  the  cover-glass  face  downward  for  twenty-four  hours. 

2  Vereins-Beilage  der  Deut.  med.  Woch.,  1895,  Bd.  148. 

3  "  Bothriocephalus-Anaemia,  "  Berlin,  1894  (Hirschwald). 


384  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

not  been  already  described  under  pernicious  anaemia  or  severe 
symptomatic  anaemia. 

ASCARIS  LUMBRICOIDES. 

The  reports  of  Jenner's  Hospital  at  Berne  for  1890  include 
a  case  in  which  the  blood  showed  only  2,450,000  red  cells  before 
driving  out  the  parasite  with  santonin,  and  4,200,000  two  weeks 
later. 


CHAPTEK  XII. 

THE  BLOOD  IN   INFANCY. 

I.  All  the  signs  by  which  sickness  is  shown  in  the  blood  of  adults 
are  exaggerated  in  children.     Their  blood  is  apparently  more 
sensitive  to  the  action  of  any  morbid  influence.     Causes  leading 
to  but  slight  anaemia  or  leucocytosis  in  the  adult,  produce  grave 
anaemia  and  very  marked  leucocytosis  in  children.     Into  the 
reasons  for  this  I  shall  not  attempt  to  enter.     The  increased 
toxicity  of  their  serum  compared  to  that  of  adults,  and  the  rela- 
tively recent  establishment  of  the  functions  for  producing  and 
destroying  blood  have  been  suggested  as  explanation. 

Comparatively  slight  hemorrhages,  gastro-intestinal  or  re- 
spiratory disorders,  which  would  not  impoverish  an  adult's  blood 
may  produce  considerable  anaemia  in  a  young  child. 

II.  All  forms  of  anaemia  in  infancy  are  apt  to  be  associated 
witli  enlarged  spleen. 

III.  I  have  already  alluded  to  the  polycythaemia  and  leucocy- 
tosis of  the  new-born,  and  the  gradual  fading  out  of  these  rela- 
tive abnormalities  as  the  child  grows  up.     In  judgments  as  to 
the  presence  or  absence  of  leucocytosis  in  infancy,  these  physio- 
logical variations  are  too  often  lost  sight  of,  especially  as  the 
proper  leucocyte  count  for  any  given  infant  depends  not  simply 
on  its  age  but  on  the  backwardness  or  forwardness  of  its  develop- 
ment.    As  with  the  fontanelles,  the  growth  of  the  blood  toward 
adult  conditions  may  be  retarded  by  congenital  weakness  (infan- 
tile atrophy,  marasmus)  or  inherited  disease  (tuberculosis,  syph- 
ilis) as  well  as  by  acquired  sickness  (rickets,  cholera  infantum). 

Under  the  influence  of  any  of  these  drawbacks  a  sick  child's 
blood  may  be  no  further  developed  at  three  years  than  that  of  a 
healthy  child  of  eighteen  months. 

IV.  When  we  remember  that  in  early  infancy  the  leucocytes 
differ  from  those  of  adults  not  only  in  number  but  in  that  the 
lymphocytes  are  relatively  more  numerous  ("  lymphocy tosis  of 
infancy"),  we  shall  understand  that  any  influence  like  rickets 

25 


386  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

or  syphilis  which  retards  development,  will  show  lymphocytosis 
together  with  the  increased  leucocyte  count.  Qualitatively  as 
well  as  quantitatively  the  blood  reverts  to  a  more  infantile  con- 
dition. 

V.  This  shows  itself  not  merely  in  the  leucocytes  but  in  the 
red  corpuscles.     During  the  first  days  after  birth  the  infant's 
blood  shows  greater  variations  in  size  and  shape  than  that  of 
adults,  as  if  the  type  were  not  yet  quite  fixed.     The  majority  of 
authors  also  find  a  few  normoblasts  in  the  first  few  days  of  life. 
These  are  not  invariably  present,  doubtless  because  in  some 
children  the  blood  at  the  time  of  birth  is  more  developed  than 
in  others. 

Under  pathological  conditions  the  red  cells  revert  to  this 
earlier  type  and  deformed  or  nucleated  corpuscles  are  plentiful. 
This  is  more  marked  than  in  anaemia  of  the  same  grade  oc- 
curring in  adults.  An  anaemia  that  shows  but  thirty  nucleated 
erythrocytes  per  cubic  millimetre  in  an  adult  might  show  ten 
times  that  number  in  a  child. 

VI.  As  we  said  before,  all  blood  changes  are  exaggerated  in 
infancy.     This  includes  such  physiological  changes  as  the  diges- 
tion leucocytosis  or  that  following  cold  bathing  as  well  as  patho- 
logical leucocytosis  and  anaemia,  and  changes  in  the  degree  of 
dilution  or  concentration  of  the  blood  seem  to  be  similarly  exag- 
gerated, as  is  seen,  e.g.,  in  the  physiological  variations  in  the 
specific  gravity  of  the  serum  (Hock  and  Schlesinger1) . 

VII.  The   haemoglobin,  though  relatively  high  at  birth  and 
for  the  first  few  weeks,  is  lower  than  that  of  adults  during 
the  rest  of  childhood.      The  high  percentages  of  the  earliest 
weeks  are  not  due  to  a  polycythaemia,  but  to  a  genuine  in- 
crease of  haemoglobin  in  the  individual  cells    (Schiff2),  color 
indexes  being  often  over  1. 

It  is  indispensable,  therefore,  that  we  should  know  the  age 
and  degree  of  development  of  a  child  before  we  can  draw  accurate 
inferences  from  its  blood.  In  many  of  the  cases  reported  in  lit- 
erature we  are  unable  to  judge  whether  the  blood  condition  is 
pathological  or  not,  because  the  age  of  the  child  is  not  given. 
For  example,  v.  Limbeck3  quotes  a  case  of  acute  gastritis  re- 

1  Hock  and  Schlesinger    Centralb.  f.  klin.  Med.,  1891. 
2Schiff :  Zeit.  f.  Heilk.,  vol.  xi.,  1890. 
3v.  Limbeck:  loc.  cit.,  p.  373. 


THE   ANAEMIAS   OF   INFANCY.  387 

ported  by  Fischl '  as  having  an  unusually  high  percentage  of 
ij  liipnoc.y  tes  (ijtfA  percent).  But  this  is  physiological  in  the 
first  days  of  life,  and  may  have  been  so  in  this  case,  the  age  not 
being  given. 

Observations  of  this  sort  should  always  represent  a  compari- 
son between  the  conditions  present  before  and  during  the  sick- 
ness in  question. 

Bearing  these  general  considerations  in  mind,  we  shall  be 
better  able  to  find  our  way  among  the  complications  and  per- 
plexities of  the  blood  conditions  in  infancy. 


THE  ANJEMIAS  OF  INFANCY. 

As  above  mentioned,  anaemic  infants  are  apt  to  have  enlarged 
spleens.  This  may  be  due  either  to  the  anaemia  or  to  some 
disease  accompanying  or  underlying  the  anaemia  (e.g.,  rickets, 
syphilis).  It  seems  more  probable  that  the  hypertrophy  is  not 
directly  or  exclusively  dependent  on  the  anaemia,  inasmuch  as 
similar  blood  changes  are  found  without  splenic  enlargement. 
By  far  the  greater  number  of  reported  cases  of  severe  infantile 
anaemia  are  accompanied  or  caused  by  such  diseases  as  rickets 
and  hereditary  syphilis,  both  of  which  may  cause  splenic  hy- 
perplasia  even  when  no  anaemia  is  present.  It  seems  probable 
that  the  anaemia  and  the  enlargement  of  the  spleen  are  alike 
symptomatic  of  an  underlying  disorder. 

1.  Some  writers  (e.g.,  Luzet2)  divide  the  anaemias  of  infancy 
into  two  classes :  those  with  splenic  enlargement  and  those  with- 
out it.     Luzet  considers  that  the  former  class  is  severer  than 
the  latter  and  more  apt  to  show  large  numbers  of  nucleated  red 
corpuscles  than  those  with  normal-sized  spleens.     This  classi- 
fication, however,  does  not  always  hold.     We  may  have  very 
severe  anaemia  without  splenic   enlargement  and  splenic   en- 
largement with  slight  anaemia,  and  the  presence  or  absence  of 
numerous  nucleated  red  corpuscles  is  governed  by  conditions 
other  than  the  size  of  the  spleen. 

2.  Another  classification  of  children's  anaemias  was  proposed 
in  1892  by  Monti  and  Berggriin  ("Die  chronische  Anamie  im 
Kindesalter,"  Leipzig,   1892).      They  divided  the  cases    into 

1  Fischl :  Zeit.  f.  Heilk.,  1892.          2  Luzet :  Diss.,  Paris,  1891. 


388 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


the  mild  and  the  grave,  each  group  being  subdivided  into  those 
with  leucocytosis  and  those  without  it. 

C  ivriri  _     j  With  leucocytosis. 

{  Without  leucocytosis. 
Secondary  anaemia  of  infancy  =  •<  ,  _„.  ,  , 

n          _  j  With  leucocytosis. 

~  (  Without  leucocytosis. 


They  rightly  discard  the  term  "  splenic  anaemia,"  correspond- 
ing as  it  does  to  no  single  set  of  blood  changes.  The  above 
classification  puts  pernicious  anaemia,  leukaemia,  and  anaemia 
infantum  pseudoleukaemica  (v.  Jaksch)  in  a  different  category. 

(a)  Mild  cases  of  secondary  anaemia  show  no  deformities  in 
the  shape  or  size  of  the  red  cells.     The  color  index  may  or  may 
not  be  low.     The  cases  with  leucocytosis  are  much  more  numer- 
ous than  those  without  it  and  more  apt  to  have  a  low  color  index  ; 
in  other  words,  the  loss  of  corpuscle  substance  is  greater  and 
the  cases  are  approaching  the  imaginary   boundary   between 
"mild"  and  "grave." 

(b)  The  grave  cases   have  poikilocytosis,    and  of  course  a 
greater  reduction  of  corpuscle  substance. 

"  Chlorotic"  conditions,  and  most  but  not  all  those  with  en- 
larged spleen,  come  under  this  heading  ;  also  most  of  those  due 
to  hereditary  syphilis,  prolonged  diarrhoea,  and  rickets. 

In  1894  Monti  !  gave  the  following  classified  lists  of  the  com- 
monest antecedents  of  secondary  anaemia  in  infancy  : 


In  the  mother  during  pregnancy. 


due  to....   |  Malada  etc 


2.  Acquired 


f  From  navel. 
ri    TT-  J  After  circumcision. 

[emorrhage.  j  Scurvy    purpura,  haemophilia,  Werl- 
[      hnf  's  disease,  meleena. 

f  Inanition. 

Bad  hygiene  (lack  of  light,  air,  etc.). 
Post-febrile. 

Nephritis,  diarrhoea,  serous  effusions. 
^  2.  Other  causes.  •{  Syphilis. 
Rickets. 
Suppuration. 

Diseases    of    liver,    spleen,    bone,    or 
^      lymph  glands. 

He  points  out  that  cases  with  leucocytosis  are  usually  graver 
than  those  without  it  and  may  develop  into  pernicious  anaemia ; 
1  Wiener  med.  Woch.,  1894. 


THE   ANAEMIAS   OF   INFANCY.  389 

also  that  the  presence  of  leucocytosis  does  not  point  to  malig- 
nant disease,  suppuration,  or  any  of  the  causes  which  usually 
account  for  it  in  adults. 

Grave  cases  with  leucocytosis  in  infants  under  twelve  months 
are  apt  to  develop  into  the  anaemia  infantum  pseudoleukaemica, 
or  into  true  leukaemia  or  pernicious  anaemia. 

On  the  whole,  the  division  of  Monti  and  Berggriin  seems 
much  better  than  that  according  to  the  particular  causes,  e.g., 
"rachitic  anaemia,"  "syphilitic  anaemia,"  etc.,  for  there  is  no 
particular  set  of  blood  changes  that  follows  rickets,  syphilis,  or 
any  other  disease.  In  connection  with  various  diseases  of  in- 
fancy, and  particularly  with  those  last  named,  we  may  have 
anaemia  of  any  grade  of  severity  from  that  reducing  the  red 
cells  to  4,000,000  down  to  cases  with  only  500,000  red  cells  per 
cubic  millimetre  or  even  less.  The  worse  the  case  is  the  more 
likely  is  it  to  be  accompanied  by  leucocytosis  and  the  more  nu- 
merous will  be  the  nucleated  red  corpuscles,  always  more  numer- 
ous here  than  in  anaemia  of  adults. 

In  syphilis,  hereditary  or  acquired,  the  red  cells  may  fall  be- 
low 1,000,000  and  the  leucocytes  may  rise  as  high  as  58,000 
(Loos).  The  haemoglobin  may  be  proportionally  diminished, 
or  may  be  even  lower  than  the  percentage  of  red  cells,  so  that  a 
"  chlorotic"  condition  obtains. 

Such  cases  have  been  called  chlorosis,  but  it  seems  better  to 
confine  this  term  to  anaemia  of  unknown  origin  and  favorable 
course  occurring  in  women  soon  after  puberty,  since  obviously 
secondary  cases  may  have  similar  blood. 

Rickets  in  a  case  observed  by  v.  Jaksch  caused  a  fall  of  the 
red  cells  to  750,000  and  Luzet  counted  1,590,000  in  a  similar 
case.  The  haemoglobin  is  usually  low,  but  Hock  and  Schles- 
inger  found  60  per  cent  with  2,300,000  red  cell,  a  color  index  of 
1.2 +. 

Leucocytosis  may  occur  even  when  no  anaemia  is  present. 
Hock  and  Schlesinger  found  45,000  leucocytes  in  a  rachitic  child 
of  sixteen  months,  sound  in  other  respects  and  not  anaemic. . 
Acute  gastritis  causes  at  first  only  leucocytosis  (with  increased 
percentage  of  lymphocytes).  If  it  becomes  chronic  the  reduction 
of  red  cells  is  severe.  Hay  em  found  only  685,000  red  cells  per 
cubic  millimetre  in  an  infant  of  two  months,  though  recovery 
eventually  took  place. 


390  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

In  tuberculosis  of  lungs  and  peritoneum  in  a  child  of  seven, 
Monti  and  Berggriin  counted  3,230,000  red  and  17,200  white 
cells  with  52  per  cent  of  haemoglobin. 

Qualitative  Changes. 

The  exaggeration  characteristic  of  all  blood  changes  in  in- 
fancy extends  to  the  presence  of  nucleated  red  corpuscles,  which 
in  all  forms  of  severe  anaemia  are  very  numerous.  What  has 
been  described  above  (page  91)  as  the  typical  megaloblast,  a 
large  pale-stained  nucleus  in  a  very  large  cell  (see  Plate  IV.),  is 
relatively  rare  in  infancy.  The  nuclei  are  almost  always  deeply 
stained  whatever  their  size,  and  apt  to  be  small.  Dividing 
nuclei  are  very  common,  both  by  karyolysis  and  karyokinesis. 
These  changes  are  most  often  found  in  the  anaemias  of  the 
severest  type  and  those  which  resemble  leukaemia  (see  below, 
page  397),  but  may  occur  in  any  marked  secondary  anaemia. 
Polychromatophilic  and  "  degenerative"  changes  are  very  com- 
mon in  severe  cases. 

The  increased  leucocyte  count,  so  frequently  fouud,  is  often 
made  up  of  a  majority  of  lymphocytes.  This  change,  as  above 
said,  is  not  characteristic  of  rickets,  syphilis,  or  any  other  cause 
of  anaemia,  but  it  is  to  be  regarded  as  a  mark  of  the  arrest  of 
development  or  reversion  to  an  earlier  type  of  tissues  brought 
about  by  various  diseases  in  early  infancy.  Sometimes  the 
large  lymphocytes  and  sometimes  the  small  are  in  excess. 

A  further  qualitative  change  already  alluded  to  (see  above, 
page  121)  is  the  occurrence  of  myelocytes.  We  have  seen  that 
small  percentages  of  these  cells  are  not  uncommonly  seen  in  the 
anaemias  of  adults.  Now  this,  like  all  other  blood  changes,  is 
exaggerated  in  infancy.  Myelocytes  are  more  apt  to  appear  and 
in  greater  numbers.  Their  presence  is  not  characteristic  of  any 
one  disease,  but  they  are  commonest  in  the  severer  types  of 
secondary  anaemia,  such  as  those  following  syphilis  and 
rickets.  Their  significance  is  about  the  same  as  that  of  nor- 
moblasts.  At  times,  however,  they  are  so  numerous  as  to 
make  us  hesitate  somewhat  before  we  exclude  splenic-myelo- 
genous  leukaemia. 

This  brings  us  naturally  to  the  discussion  of  the  difficulty  of 
distinguishing  the  different  blood  diseases  in  infancy,  which  natur- 


"ANEMIA  INFANTUM  PSEUDOLEUK^EMICA."  391 

ally  centres  in  the  question  of  the  existence  and  nature  of  the 
so  called 

"ANEMIA  INFANTUM  PSEUDOLEUK^EMICA." 

Von  Jaksch's1  decription  of  this  disease  (which  he  was  the 
first  to  recognize)  includes  the  following  elements : 

1.  Grave  anaemia— e.g.,  820,000  red  cells  per  cubic  millimetre 
in  one  case. 

2.  Extensive  leucocytosis— e.g.,  54,660  white  cells  per  cubic 
millmetre,  in  the  same  case. 

3.  Great  variations  in  the  form,  size,  and  staining  of  the 
white  cells. 

4.  Deformed,  degenerated,  and  nucleated  red  cells. 

Von  Jaksch  admits  that  none  of  these  blood  changes  are 
characteristic  of  the  disease,  but  thinks  that  its  title  to  the  posi- 
tion of  a  distinct  and  separate  disease  rests  upon  clinical  data, 
the  more  important  of  which  are :  (1)  A  great  enlargement  of 
the  spleen  without  any  such  accompanying  enlargement  of  the 
liver  as  is  usually  found  in  leukaemia  (the  lymph  glands  are 
sometimes  enlarged).  (2)  A  relatively  good  prognosis.  (3)  Post 
mortem  we  find  no  positive  evidence  of  leukaemia. 

This  description  was  given  by  v.  Jaskch1  in  1889.  He  stated 
the  relation  of  white  to  red  corpuscles  as  1 : 12,  1 : 17,  and  1 : 20 
in  the  cases  seen  by  him.  Later  he  reported  three  cases  in  one 
of  which  the  white  cells  numbered  114,150,  and  the  red  1,380,- 
000.  The  differential  counts  are  not  carefully  given. 

Almost  at  the  same  time  Hayem*  reported  a  similar  case, 
and  noted  the  abundance  of  nucleated  red  corpuscles  many  of 
which  were  undergoing  mitosis.  This  was  verified  by  Luzet 3 
in  May,  1891  (Arch.  gen.  de  Med.),  who  reported  two  cases. 
His  description  of  the  disease  differs  considerably  from  that  of 
v.  Jaksch.  He  finds  no  greater  difference  between  liver  and 
spleen  than  often  exists  in  true  leukaemia.  The  course  of  the 
disease,  though  sometimes  chronic,  usually  ends  in  death.  The 
leucocytosis  in  Luzet' s  cases  was  less  marked  than  in  those  of  v. 
Jaksch  and  not  greater  than  that  occurring  in  many  anaemias 
of  children.  He  dwells  particularly  on  the  large  number  of  nu- 

'  Von  Jaksch  .-  Wien.  klin.  Wocli.,  1889,  Nos.  22,  23. 

2  Hayem    Gaz.  des  Hopitaux,  1889,  No.  30. 

3  Luzet :  Diss. ,  Paris,  1891. 


092  SPECIAL    PATHOLOGY   OF   THE   BLOOD. 

cleated  red  cells,  and  the  frequency  of  mitosis  and  considers  this 
the  most  important  diagnostic  point. 

Although  Luzet's  continues  to  use  the  name  suggested  by  v. 
Jaksch,  he  describes  the  disease  so  differently  that  it  is  difficult 
to  see  why  the  same  title  should  be  given  to  it.  He  agrees  with 
v.  Jaksch  in  thinking  that  it  is  not  simply  a  severe  secondary  anae- 
mia due  to  syphilis,  rickets,  tuberculosis,  or  infectious  disease. 

Somewhat  similar  cases  had  already  been  described  by  vari- 
ous Italian  writers  (e.g.,  Fede)  under  the  title  of  "Infective 
Splenic  Anaemia  of  Infants." 

Among  others  who  have  written  on  the  subject  are  Baginsky,1 
Senator,2  Fischl,3  Andeoud,4  Monti  and  Berggriin,5  Felsenthal,6 
Baudnitz,7  Epstein,8  Alt  and  Weiss,9  Hock  and  Schlesinger,10 
Crocq,11  and  Botch.12 

The  majority  of  these  writers  report  very  little  as  to  the  dif- 
ferential counts  of  white  corpuscles.  An  increased  percentage 
of  the  polymorphonuclear  forms  is  mentioned  by  many,  but 
Botch  in  a  case  with  1,311,250  red  cells  and  116,500  white  cells 
found  only  16  .per  cent  of  the  polymorphonuclear  variety  with 
46  per  cent  of  small  lymphocytes,  34  per  cent  of  large  lympho- 
cytes, and  4  per  cent  eosinophiles.  A  second  case  had  only  14 
per  cent  of  polymorphonuclear  cells  and  84  per  cent  of  lympho- 
cytes (large  and  small). 

Von  Jaksch  noted  the  lack  of  any  relative  increase  of  eosino- 
philes, supposing  this  to  be  a  means  of  distinguishing  his  cases 
from  true  leukaemia.  Luzet,  on  the  other  hand,  found  eosino- 
philes numerous.  (This  of  course  has  no  weight  for  or  against 
leukaemia. ) 

Klein  (loc.  cit.)  noted  the  occurrence  of  myelocytes  in  small 
number. 

I  Baginsky:  Arch.  f.  Kinderheilk.,  1892,  vol.  13. 
*  Senator:  Berlin,  klin.  Woch.,  1892. 

3  Fischl :  loc.  cit. 

4  Andeoud  :  Rev.  de  med.  de  la  Suisse  rom.,  1894,  p.  507. 
6  Monti  and  Berggriin  :  loc.  cit. 

6  Felsenthal :  loc.  cit. 

7  Raudnitz:  Prag.  med.  Woch.,  1894,  p.  6. 

8  Epstein:  Prag.  raed.  Woch.,  1894,  p.  6. 

9  Alt  and  Weiss :  Centralb.  f .  med.  Wissenschaft,  1892. 

10  Hock  and  Schlesinger  :  loc.  cit. 

II  Crocq:  "Etude  sur  1'Adenie,"  etc.,  Brussels,  1891  (Lamartin). 
12  Rotch  :  Psediatrics,  1895,  p.  361. 


"ANEMIA   INFANTUM   PSEUDOLEUKAEMICA."  393 

The  discrepancy  of  these  different  reports  is  suggestive. 

The  chief  importance  of  the  heterogeneous  group  of  cases 
which  have  received  the  name  of  anaemia  infantum  pseudoleu- 
kcemica  seems  to  me  to  be  as  a  proof  of  the  difficulty  of  distin- 
guishing the  various  blood  diseases  in  infancy. 

Among  the  cases  reported  under  this  name  are  some  which 
might  be  any  one  of  the  following  list:  Pernicious  anaemia, 
secondary  anaemia  with  leucocytosis,  Hodgkin's  disease,  lym- 
phatic leukaemia,  and  probably  splenic-myelogenous  leukaemia. 

(a)  Most  of  the  few  reported  cases  of  pernicious  anaemia  in 
infancy  have  shown  moderate  leucocytosis  (as  compared  with 
adult  blood),  a  fact  which  deprives  us  of  one  of  the  means  of  dis- 
tinguishing the  disease  from  secondary  anaemia.  The  reports 
as  to  nucleated  corpuscles  very  rarely  separate  normoblasts  from 
megaloblasts,  and  we  have  no  way,  therefore,  of  being  sure  on 
this  important  point.  The  high  color  index  and  large  diameter 
of  the  red  cells  are  occasionally  seen  in  other  anaemias  of  infancy 
and  are  not  always  present  in  pernicious  cases.  The  great 
fatality  of  all  kinds  of  anaemia  in  infancy  prevents  our  calling  a 
case  pernicious  because  of  a  fatal  termination.  Enlargements  of 
liver  and  spleen  occur  in  many  cases  of  each  type  of  infantile 
anaemia,  and  occasionally  in  pernicious  anaemia  of  adults.  They 
do  not,  therefore,  exclude  pernicious  angcmia  in  infancy. 

Bearing  these  facts  in  mind,  it  is  evident  that  some  of  Luzet's 
cases  of  "anaemia  infantum  pseudoleukaemica"  may  have  been 
pernicious  anaemia.  Von  Jaksch's  own  cases  may  have  been 
either  (a)  Hodgkin's  disease  with  leucocytosis,  (I)  grave  secon- 
dary anaemia  with  leucocytosis  (Monti  and  Berggriin),  or  (c) 
leukaemia. 

(a)  Hodgkin's  disease,  which  v.  Limbeck  finds  to  be  very 
common  in  infancy,  may  affect  the  liver  and  spleen  and  not  the 
external  lymph  glands,  and  may  be  accompanied  by  anaemia 
and  leucocytosis  such  as  v.  Jaksch  describes.  Epstein  con- 
siders that  this  is  the  case,  and  denies  the  existence  of  any  such 
disease  as  the  anaemia  infantum  pseudoleukaemica. 

(&)  As  any  anaemia  secondary  to  rickets  or  syphilis  may  have 
enlarged  spleen  and  liver  and  marked  leucocytosis,  we  cannot 
tell  from  v.  Jaksch's  description  that  we  are  not  dealing  in  his 
cases  with  secondary  anaemia. 

(c)  Since  v.  Jaksch  does  not  give  any  accurate  differential 


394  SPECIAL    PATHOLOGY    OF   THE   BLOOD. 

count  of  the  leucocytes,  there  may  have  been  large  numbers  oi 
myelocytes  in  his  cases  for  all  we  know,  or  an  overwhelming 
percentage  of  lymphocytes,  i.e.,  either  type  of  leukaemia. 

One  of  the  cases  reported  by  Rotch  as  "  anaemia  infantum 
pseudoleukaemica"  had  80  per  cent  of  lymphocytes  in  a  leucocyte 
count  of  116,500,  the  ratio  of  white  to  red  cells  being  1:11,  and 
the  nucleated  corpuscles  abundant.  The  external  lymph  glands 
as  well  as  the  liver  and  spleen  were  enlarged.  How  such  a  case 
is  to  be  distinguished  from  lymphatic  leukaemia  without  autopsy 
I  cannot  see.  Large  numbers  of  nucleated  corpuscles  with  mito- 
ses (present  in  this  case)  are  to  be  found  in  any  anaemia  of  in- 
fancy where  the  red  cells,  as  in  this  case,  have  sunk  as  low  as 
1,311,500,  and  therefore  do  not  exclude  leukaemia. 

Von  Jaksch  protests  that  his  cases  are  not  secondary  to 
rickets  or  any  other  disease,  but  Fischl 1  in  a  careful  study  of  all 
the  published  cases  finds  that  out  of  a  total  of  eighteen  cases, 
sixteen  had  severe  rickets  and  two  hereditary  syphilis. 

The  writings  of  Eaudnitz,  Ebstein,  Felsenthal,  Fischl,  and 
v.  Limbeck,  which  deny  the  separate  existence  of  the  anaemia 
infantum  pseudoleukaemica,  are  convincing  to  me,  and  are  rein- 
forced by  the  few  cases  of  bad  anaemia  in  children  which  I  have 
seen.  We  must  distribute  the  cases  of  anaemia  with  leucocy- 
tosis  and  large  spleen  under  pernicious  anaemia,  secondary  an- 
aemia, and  leukaemia. 

But  our  problem  is  not  yet  nearly  solved.  All  we  have 
gained  is  the  belief  that  v.  Jaksch's  new  disease  does  not  help  us 
to  classify  these  doubtful  cases.  The  difficulty  is  still  very  great. 
The  following  cases  reported  by  Dr.  Vickery  in  the  Medical 
News  for  December,  1897,  illustrate  this : 

CASE  I. — A  male  child  of  sixteen  months  with  symptoms  of 
grave  anaemia,  greatly  enlarged  spleen  and  slightly  enlarged 
liver,  showed  the  following  figures:  Eed  cells,  2,500,000;  white 
cells,  22,000.  Differential  count  of  500  cells  showed:  Lym- 
phocytes, 53.8  per  cent  (46.2  of  the  smaller  type) ;  polymor- 
phonuclear  cells,  29.4  per  cent;  eosinophiles,  6.2  per  cent; 
myelocytes,  10  per  cent. 

While  counting  these,  147  nucleated  red  corpuscles  were 
seen,  of  which  21  were  normoblasts,  50  megaloblasts,  and  47 
microblasts ;  6  showed  mitosis  in  their  nuclei. 

The  child  died  shortly  after  without  any  complication  or 

1  Fischl    Zeit.  f.  Heilkunde,  1892. 


395 

intercurreut  disease.  No  autopsy.  No  evidence  of  rickets  or 
syphilis  or  other  previous  disease. 

CASE  II. — Young  infant  with  enlarged  external  lymph  glands 
and  very  large  spleen.  July  14th,  1897— Eed  cells,  4,300,000; 
white  cells,  31,000;  haemoglobin,  60  per  cent;  polymorpho- 
nuclear  neutrophiles,  57.5  per  cent;  small  lymphocytes,  26  per 
cent;  large  lymphocytes,  15  per  cent;  eosinophiles,  0.5  per  cent; 
myelocytes,  1  per  cent. 

One  or  two  nucleated  red  corpuscles  in  every  field.  Out  of 
100  of  them  89  were  large  and  11  small.  Many  showed  mitosis. 
Polychromatophilic  forms  numerous.  July  19th — Seventeen 
megaloblasts  seen  while  counting  1,000  white  cells.  Blood  is 
otherwise  about  the  same.  The  case  was  lost  sight  of  and  not 
traced. 

Now  I  see  no  reason  for  supposing  these  cases  to  represent 
a  new  type  of  disease,  and  yet  I  cannot  feel  perfectly  safe  in 
classifying  them  as  primary  anaemia,  secondary  anaemia,  or  leu- 
kaemia. 

(a)  Primary  or  pernicious  anaemia  should  have  a  lower  count 
of  red  cells.     The  percentage  of  myelocytes  in  the  first  case 
(ten  per  cent)  is  higher  than  in  any  other  case  of  pernicious 
anaemia  on  record,  though  in  one  adult  case  with  autopsy  I 
found  9.2  per  cent  with  a  leucocytosis  of  12,500,  or  1,150  mye- 
locytes per  cubic  millimetre,  against  2,200  per  cubic  millimetre 
in  this  case. 

(b)  It  is  hard  to  call  an  anaemia  secondary  which  kills  with 
no  complications  and  when  there  is  no  evidence  of  any  disease 
to  which  it  can  be  secondary. 

(c)  For  splenic-myelogenous  leukaemia  the  total   leucocyte 
count  and  the  percentage  of  myelocytes  are  very  small  in  either 
case.     Still  the  leucocyte  count  may  drop  very  low  in  leukaemia 
even  without  any  inflammatory  complication.     Such  a  case  is 
reported  by  Osier,  in  which  the  leucocytes  fell  to  7,500,  of  which 
only  300,  or  four  per  cent,  were  myelocytes. 

Hay  em  (loc.  cit.,  page  864)  in  a  ten  months'  child  counted 
2,712,500  red  and  33,000  white  cells,  almost  the  same  figures 
as  in  the  case  just  quoted.  [Hay em  unfortunately  gives  no 
differential  count,  but  apparently  considers  the  case  leukaemia 
because  of  the  enormous  number  of  nucleated  red  cells,  many 
with  mitoses.] 

Morse's  case  of  leukaemia  in  infancy  had  2,900,000  red  and 
48.000  white  cells.  Twenty -one  and  four-tenths  per  cent  of  the 


396  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

leucocytes,  or  about  10,000,  were  myelocytes.  The  same  abun- 
dance of  nucleated  red  cells  (some  with  mitoses)  were  here  pres- 
ent as  in  Hay  em's  case,  so  that  there  is  evidently  nothing  pecu- 
liar in  their  presence  in  the  disease  described  by  v.  Jaksch,  as 
Luzet  supposed. 

These  cases  show  that  leukaemia  may  at  certain  periods  pre- 
sent just  such  a  blood  picture  as  was  present  in  the  above-quoted 
case  and  that  the  number  of  leucocytes  in  the  leukaemia  of  in- 
fants may  be  no  greater  than  that  in  any  anaemia  with  the  leu- 
cocytosis  so  common  in  children. 

It  seems  to  me  the  most  natural  conclusion  to  be  deduced 
from  these  facts  is  that  we  meet  with  cases  in  infancy  which  are 
apparently  intermediate  betiveen  leukaemia  and  pernicious  ancemia. 
I  have  pointed  out  elsewhere  that  there  are  many  points  of  re- 
semblance between  the  two  diseases.  The  case  of  leukaemia  re- 
ported by  Osier  showed  at  one  period — the  period  of  remis- 
sion— a  fall  in  the  number  of  leucocytes  and  in  the  percentage 
of  myelocytes  till  the  blood  was  practically  that  of  pernicious 
anaemia. 

Dr.  Kotch's  case  (above  quoted)  is  another  in  which  the  diag- 
nosis seems  to  lie  somewhere  intermediate  between  the  two 
diseases,  anaemia  and  leukaemia. 

The  case  which  I  have  quoted  above  seems  to  me  on  the 
whole  nearer  to  the  type  of  pernicious  anaemia  than  of  leukaemia, 
and  Dr.  Botch's  nearer  to  the  latter  than  to  the  former;  but  each 
is  really  intermediate,  so  far  as  the  blood  goes,  between  the  two 
diseases.  I  have  no  intention  of  suggesting  that  the  organic 
lesions  in  these  cases  are  intermediate  between  leukaemia  and 
pernicious  anaemia.  It  is  simply  the  blood  that  is  so. 

Engel's  case,  reported  in  Yirchow's  Archiv,  Vol.  135,  sug- 
gests the  same  thing.  He  calls  the  case  one  of  "pseudo-perni- 
cious anwmia."  Meylocytes  were  abundant. 

PolymorpJious  Condition. 

This  illustrates  that  "  polymorphous"  condition  of  the  blood 
which  v.  Jaksch  supposed  to  be  characteristic  of  the  anaemia  in- 
fantum  pseudoleukaemica.  The  same  thing  was  very  marked  in 
all  the  bad  cases  of  anaemia  which  I  have  seen,  including 
the  case  above  mentioned,  and  a  case  of  true  leukaemia  in 
a  girl  of  eight.  The  impression  one  gets  from  the  field  of  a 


LEUKAEMIA.  397 

stained  specimen  is  that  no  two  white  corpuscles  are  alike.  Every 
species  is  subdivided  into  several  sub-varieties  and  all  stages  of 
degeneration  are  to  be  seen  in  each  variety.  But  this  is  char- 
acteristic of  any  very  severe  infantile  anaemia  and  not  of  any 
single  type. 

LEUKEMIA. 

In  Morse's  careful  article  of  August,  1894  (Boston  Med.  and 
Surg.  Journal} ,  twenty  cases  of  leukaemia  in  infancy  are  collected. 
As  he  rightly  says,  probably  most  of  these  cases  were  not  gen- 
uine. Only  one  of  them  includes  a  differential  count,  and  this  is 
in  a  lymphatic  case.  Morse's  is  the  only  one  of  the  splenic- 
myelogenous  type  on  record  in  which  the  diagnosis  is  made 
reasonably  certain  by  a  color  analysis.  Fischl  in  1892  said  that 
there  was  no  case  on  record  with  a  differential  count. 

A  case  was  seen  in  1890  by  Dr.  F.  C.  Shattuck,  which  was 
apparently  acute,  the  symptoms  appearing  only  six  weeks  be- 
fore death.  Cover-glass  preparations  examined  by  W.  S.  Thayer 
showed  a  ratio  of  about  1  white  to  20  red  cells.  The  differ- 
ential count '  showed:  Small  lymphocytes,  97.9  per  cent;  large 
lymphocytes,  .7  percent;  poly  nuclear  cells,  1.4  per  cent;  eosino- 
philes,  .08  per  cent. 

The  other  case  reported  by  Morse  has  been  mentioned 
above. 

Charon  and  Giratea "  have  recently  reported  a  case  in  a  child 
of  eight  with  880,000  red  cells,  305,000  white  cells,  and  39  per 
cent  of  haemoglobin.  It  was  apparently  of  the  myelocyte  type. 
E.  Miiller  thinks  that  there  are  about  five  other  (German)  cases 
on  record,  all  of  acute  leukaemia  and  all  with  a  similar  blood 
count,  though  in  some  the  large  lymphocytes  (without  neutro- 
philic  granules)  have  been  described  as  "myelocytes." 

Miiller 3  has  lately  reported  with  great  care  three  cases  of 
leukaemia,  all  of  them  in  boys  four  years  old— all  apparently 
acute,  all  of  the  gastro-intestinal  type — i.e.,  the  glands  and  fol- 
licles throughout  the  whole  length  of  the  alimentary  tract  being 

1  Reported  by  Thayer  in  the  Boston  Medical  and  Surgical  Journal,  189P, 
vol.  128,  p.  183. 

2 Bull.  d.  Soc.  Roy.  d.  Sciences  Med. ,  etc.,  Bruxelles,  1897,  No.  7. 
3  Jahrbuch  fiir  Kinderheilk.,  1896,  vol.  43. 


398 


SPECIAL   PATHOLOGY   OF   THE    BLOOD. 


the  chief  seats  of  infiltration,  though  the  liver  and  spleen  were 
also  enlarged.     The  counts  were  as  follows : 


CASE  I. 

CASE  II. 

CASE  III. 

April 
30th. 

«*!* 

May  2d. 

May  3d. 

Red  cells  

1,508,000 
109,500 

1,684,000 
93,800 

1,362,000 
46,000 

1,232,000 
6,800 
Death. 

2,290,000 
206,000 

1,308,000 
420,000 

White  cells  
Haemoglobin 

Polymorphonuc  1  e  a  r 
neutrophiles    . 

85£  (8-10  M  diameter). 
1* 

Many. 
Few. 
Few. 
Many. 

1& 

.7 
2. 
97.3 
.01 

Small  lymphocytes1.  . 
Large  lymphocytes  .  . 
Eosinophiles 

Few. 
Few. 

Two  nor  mo  - 
blasts  seen  in 
counting 
1,135  1  e  u  - 
cocytes. 

Seven    seen   in 
counting  1,118 
leucocytes. 

Megaloblasts  

All  with  large  pale  nuclei. 


APPENDIX. 


NEUSSER'S  PERINUCLEAR  BASOPHILIC  GRANULES. 

Using  the  following  modificatiou  of  Ehrlich's  tricolor  mix- 
ture, Neusser1  believes  that  he  can  bring  out  certain  character- 
istics in  the  leucocytes  of  value  in  diagnosis  and  prognosis. 

i  Acid  f  uchsin 50  c.  c. 

Saturated  aqueous  solution  of  •!  Orange  G 70    " 

(  Methyl  green 80     M 

Distilled  water 150    " 

Absolute  alcohol 80    " 

Glycerin , 20    u 

Cover  slips  stained  with  this  mixture  show  in  certain  dis- 
eases (e.g.,  gout,  leukaemia)  a  grouping  of  dark  blue-stained 
granules  around  the  nuclei  of  the  mononuclear  leucocytes  and 
over  and  around  the  nuclei  of  polymorphonuclear  leucocytes. 
These  granules  appear  to  take  up  only  the  basic  part  of  the 
tri-color  mixture. 

For  Neusser's  conclusions  regarding  the  meaning  of  these 
granules,  the  reader  is  referred  to  pages  258  and  318.  The 
researches  of  Futcher  have  in  my  opinion  utterly  disproved 
Neusser's  claims.  The  granules  are  of  no  known  clinical  sig- 
nificance and  certainly  have  no  direct  relation  to  gout  or  any 
other  alloxuric  diathesis.  I  have  a  triple  stain  (not  made  up 
for  the  purpose)  which  brings  out  Neusser's  granules  in  every 
blood,  normal  or  abnormal. 

1Wien.  klin.  Woch.,  1894,  No.  39. 


PART  VII. 

EXAMINATION   OF   THE   SERUM. 


CHAPTER  XIII. 

THE      CLUMP      REACTION. 

GENERAL  DESCRIPTION. 

ALTHOUGH  this  phenomenon  is  to  be  obtained  in  various  in- 
fections, natural  as  well  as  experimental,  and  with  various  body 
fluids,  I  shall  describe  as  a  typical  case  of  it  the  reaction  which 
takes  place  when  the  blood  serum  of  a  patient  ill  with  typhoid 
fever  is  added  in  certain  proportions  (vide  infra)  to  a  young 
bullion  culture  of  well-certified  and  virulent  typhoid  bacilli.  In 
a  drop  of  such  a  mixture,  examined  between  slide  and  cover- 
glass1  with  a  magnification  of  300  diameters  or  more  (an  immer- 
sion lens  is  not  necessary) ,  we  notice,  as  soon  as  the  serum  and 
culture  are  mixed,  either  a  marked  slowing  of  the  progressive 
movements  of  the  bacilli  or  an  unequal  distribution  of  them  in 
the  different  parts  of  the  preparation,  some  parts  showing  the 
bacilli  closely  crowded,  while  in  others  they  are  more  scat- 
tered. Whichever  of  these  changes  occurs  first,  the  slowing  of 
locomotion  or  the  tendency  to  grouping,  the  other  soon  follows, 
and  then  both  processes  go  on  together,  as  admirably  described 
by  Biggs  and  Park : 2 

"  Some  of  the  bacilli  soon  cease  all  progressive  movement, 
and  it  will  be  seen  that  they  are  gathering  together  in  small 
groups  of  two  or  more,  the  individual  bacilli  being  still  some- 
what separated  from  each  other.  Gradually  they  close  up  the 
spaces  between  them,  and  clumps  are  formed.  According  to  the 

1  Hanging-drop  preparations  are  often  recommended,  but  a  simple  slide 
and  cover-glass  are  as  good  for  the  purposes  of  this  reaction. 

2  American  Journal  of  the  Medical  Sciences,  March,  1897. 


THE    CLUMP   REACTION. 


401 


completeness  of  the  reaction,  either  all  the  bacilli  may  finally 
become  clumped  and  immobilized  or  only  a  small  portion  of 
them,  the  rest  remaining  freely  motile,  and  even  those  clumped 
may  appear  to  be  struggling  for  freedom.  With  blood  contain- 
ing a  large  amount  of  the  agglutinating  substances  all  gradations 


FIG.  55.— Pure  Culture. 


FIG.  56.— Partial  Reaction. 


FIG.  57.— Typical  Clumping. 


in  the  intensity  of  the  reaction  may  be  observed,  from  those 
shown  in  a  marked  and  immediate  reaction  to  those  appearing 
in  a  late  and  indefinite  one,  by  simply  varying  the  proportion  of 
blood  added  to  the  culture  fluid"  (see  Figs.  55,  56,  and  57). 

The  process  may  go  on  gradually  and  be  much  more  distinct 
at  the  end  of  half  an  hour. 

The  groups  or  clumps  above  described  constitute  the  impor- 
tant part  of  the  reaction  for  diagnostic  purposes.     Of  the  loss  of 
motility  more  will  be  said  later. 
26 


402  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

The  clumps  may  hang  together  for  a  long  time.  They  have 
been  observed  unchanged  for  one  hundred  and  forty -four  hours. 
On  the  other  hand,  they  may  be  dissolved  in  a  few  hours  and  the 
bacilli  regain  their  motility. 

In  watching  the  formation  of  the  clumps  it  is  easy  to  see 
that  the  bacilli  are  positively  attracted  to  each  other  and  do  not 
drift  passively  into  a  heap.  The  loss  of  motility  is  not  the 
cause  of  the  clumping,  as  they  often  begin  to  approach  each 
other  while  in  vigorous  motion.  The  power  of  locomotion  is 
lost  much  sooner  than  are  the  squirming  and  spinning  motions, 
which  often  persist  among  the  bacilli  in  the  peripheral  parts  of 
the  clumps  as  well  as  outside  them. 

The  clumps  tend  to  adhere  to  the  under  side  of  the  cover- 
glass. 

Specimens  can  be  fixed  and  stained  with  the  bacilli  in  clumps 
— contrasting  strongly  with  the  even  distribution  of  the  bacilli 
in  ordinary  stained  preparations. 

TECHNIQUE  OP  THE  CLUMP  EEACTION  IN  TYPHOID  FEVER. 

Our  account  of  the  methods  of  obtaining  the  clump  reaction 
may  be  divided  into  the  following  parts : 

1.  The  body  fluids  to  be  used  and  the  methods  of  obtaining 
them. 

2.  The  cultures. 

3.  Dilution  and  the  time  limit. 

1.  THE  BODY  FLUIDS  TO  BE  USED. 

Experiments  have  proved  that  the  reaction  can  be  obtained 
with  the  following  fluids : 

(a)  The  whole  blood,  fluid  or  dried. 

(6)  The  plasma  and  serum,  fluid  or  dried. 

(c)  The  fluid  obtained  by  blistering. 

(d)  The  fluid  normally  present  in  the  pericardium,  pleura, 
peritoneum,  and  joints;  not  in  rapidly  accumulated  effusions. 

(e)  The  milk  and  colostrum  of  women  suffering  from  typhoid 
during  lactation. 

(/)  Pus  from  persons  suffering  with  typhoid— whether  the 
bacilli  of  Eberth  are  present  in  the  pus  or  not. 


THE   CLUMP   REACTION.  403 

(g)  Tears— naturally  (i.e.,  gradually)  secreted.  If  secreted 
in  response  to  the  irritation  of  ammonia  fumes,  the  tears  do  not 
produce  clumping. 

(h)  Some  observers  also  find  it  in  the  fluid  of  oedema  and  in 
the  bile.  Others  do  not. 

(i)  The  clumping  persists  in  the  above-named  fluids  after 
death  and  even  in  putrefaction.  The  "juice"  of  the  spleen, 
kidneys,  and  rarely  of  the  liver,  will  give  the  reaction  feebly. 

(/)  Though  present  in  the  placental  blood  of  pregnant 
typhoid  patients,  it  does  not  usually  exist  in  the  foetus. 

The  saliva,  gastric  juice,  and  sweat  do  not  produce  the  reac- 
tion, so  far  as  known.  The  aqueous  humor  sometimes  does. 

The  urine  and  faeces  sometimes  do  and  sometimes  do  not  give 
it,  but  these  excretions  in  normal  persons  may  also  produce  the 
reaction,  so  that  they  cannot  be  made  clinically  available. 

Of  all  these  fluids,  the  blood,  the  serum,  and  the  fluid  of 
blisters  are  the  only  ones  used  in  clinical  work,  both  because 
of  their  greater  convenience,  and  because  the  clumping  power  is 
much  more  marked  in  the  blood  and  blister  fluid  than  in  any  of 
the  others. 

1.    Use  of  the  Wliole  Blood— Fluid. 

TJie  advantages  of  this  method  are  (a)  its  quickness,  and  (6) 
the  small  amount  of  blood  (one  drop)  sufficient  for  the  test. 

Its  disadvantages  are  (a)  that  the  corpuscles  interfere  slightly 
with  the  fields  in  which  the  reaction  is  to  be  watched,  and  (b) 
that  they  sometimes  lead  to  the  formatkm  of  false  clumps 
("pseudo-amas"),  which  simulate  those  present  in  the  real 
clump  reaction,  and  lead  to  false  inferences.  Both  these  objec- 
tions are  trifling,  however,  as  the  corpuscles  can  be  excluded  by 
waiting  a  minute  or  two  until  they  settle,  leaving  a  clear  liquid 
above  in  which  the  reaction  can  be  observed.  The  false  clumps 
are  rarely  seen,  and  can  be  differentiated  from  the  true  by  care- 
ful technique  (see  below). 

I  have  used  this  method  in  many  cases  and  always  found 
it  satisfactory  and  convenient.  Widal,  McWeeney,  Delepine, 
Coleman,  and  others  have  employed  it  with  success.  It  is 
most  suitable  for  the  "  quick  method"  (see  page  406),  and  is 
chiefly  employed  in  this  way. 

Procedure. — Suck  up  some  water  with  a  medicine-dropper  and 


404  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

expel  ten  drops  of  it  into  a  watch-glass.  Then  empty  and  dry 
the  dropper,  draw  up  from  the  watch-glass  the  ten  drops  just 
expelled,  and  mark  with  a  file  on  the  side  of  the  dropper  the 
point  up  to  which  the  ten-drop  column  extends.  Mark  also  the 
point  to  which  one  drop  (expelled  and  then  sucked  up  again  as 
before)  will  rise. 

Ten  drops  of  the  bouillon  culture  of  the  bacilli  to  be  used 
are  then  expelled  into  each  of  several  small  test-tubes,  and  one 
of  these  tubes  is  carried  to  the  bedside.  After  pricking  the 
ear  as  if  for  blood  examination1  (see  page  6),  put  the  end  of  the 
medicine-dropper  into  the  blood  drop,  and  carefully  draw  back 
the  rubber  bulb  (which  has  been  previously  pushed  down  over 
the  glass  part  of  the  dropper)  until  the  blood  rises  to  the  mark 
for  one  drop.  Wipe  from  the  outside  of  the  dropper  any  blood 
that  may  adhere  there  and  then  expel  the  drop  into  one  of  the 
little  test-tubes  containing  the  ten  drops  of  bouillon  culture.  In 
this  way  blood  can  be  taken  for  examination  from  a  dozen 
patients  in  as  many  minutes. 

2.    Whole  Blood— Dried. 

This  method,  though  previously  described  and  tested  by 
Widal,  was  first  put  into  effect  in  large  numbers  of  cases  by 
Wyatt  Johnson,  of  Montreal,  for  the  use  of  the  Board  of  Health 
of  Quebec,  by  whom  specimens  of  dried  blood  sent  by  mail  were 
examined  and  diagnoses  returned  as  with  diphtheria  cultures. 
It  was  subsequently  employed  on  a  large  scale  by  the  Boards  of 
Health  of  New  York  and  Chicago. 

The  advantages  of  the  method  are  (a)  the  ease  and  quickness 
with  which  the  blood  can  be  obtained,  (b)  the  convenience  for 
transportation  by  mail,  and  (c)  that  it  does  not  deteriorate  or 
become  contaminated  by  bacterial  growth,  as  specimens  of  fluid 
blood  or  serum  are  so  apt  to  do.  Its  clumping  power  is  fully 
equal  to  that  of  the  serum  in  most  cases* 

These  advantages  are  very  great  and  would  surely  lead  to  the 

1  Squeezing  and  milking  the  ear  are  of  no  luirm  in  this  procedure  and 
enable  us  to  get  on  with  a  trifling  and  painless  puncture. 

'2  Widal  and  Delepine  think  the  fluid  serum  is  slightly  more  powerful  than 
the  dried  blood.  Johnson  admits  that  in  one-tenth  of  the  cases  the  serum  is 
the  more  powerful.  I  have  obtained  reactions  with  the  dried  blood  in  only 
seven-eighths  of  the  cases  in  which  I  got  them  with  the  fluid  serum. 


THE    CLUMP   REACTION.  405 

immediate  and  universal  adoption  of  this  method  were  it  not  for 
iiie  following  serious  drawbacks : 

(a)  It  is  difficult  to  measure  the  amount  of  blood  to  be  used  in 
the  test.     This  is  important,  because,  as  we  shall  see  later,  a 
positive  reaction  means  not  simply  a  clumping,  but  a  clamping 
in  a  1 : 10  dilution  of  the  blood,  to  get  which  we  need  to  know  just 
how  much  blood  we  are  dealing  with.     When  we  take  the  blood 
from  a  patient  ourselves  we  can  use  the  marked  medicine  drop- 
per, as  above  described,  but  when  blood  is  received  through 
the  mails  for  examination  or  taken  by  any  one  who  does  not 
measure  it  in  some  way,  we  cannot  accurately  gauge  the  dilu- 
tion. 

(b)  It  is  agreed  by  all  who  have  used  the  method  extensively 
that  the  clumping  may  occur  with  the  blood  of  healthy  people 
and  hence  confuse  our  inferences.     Whether  these  "  false  clumps" 
are  due,  as  Widal  supposes,  to  masses  of  fibrin  and  debris  in 
which  the  bacilli  become  entangled,  or  whether  they  are  formed 
in  the  ordinary  way,  there  can  be  no  doubt  that  they  occur  occa- 
sionally when  dried  blood  is  used.     Johnson  has  succeeded  in 
avoiding  such  errors  in  his  own  work  by  the  use  of  attenuated 
culture  (vide  infra). 

These  objections  have  led  most  observers  to  prefer  the  fluid 
serum,  but  when  we  have  not  the  apparatus  necessary  for  col- 
lecting and  preserving  fluid  serum,  or  when  such  apparatus 
could  not  be  transported,  the  method  is  of  great  value. 

Procedure. — The  blood  should  be  dried  either  upon  a  glass 
slide  or  on  a  piece  of  glazed  paper  or  card.  Any  absorbent 
substance  is  less  available.  Glass  is  easier  to  sterilize  than 
paper.  Several  large  drops  should  be  placed  in  different  parts 
of  the  glass  or  paper  and  thoroughly  dried. 

If  paper  has  been  used,  we  cut  out  the  dried  blood  drop  with 
a  pair  of  scissors,  keeping  close  to  the  blood  all  round,  and  drop 
it  into  a  test-tube  containing  one  or  two  drops  of  water,  in  which 
with  some  sharp-pointed  instrument  we  mix  the  dried  blood, 
freeing  it  as  well  as  possible  from  the  paper. 

To  the  liquid  so  obtained  add  eight  or  nine  drops  of  the 
bouillon  culture  of  bacilli  and  proceed  in  the  ordinary  way.  Or 
we  may  drop  the  fragment  of  paper  holding  the  blood  directly 
into  ten  drops  of  bouillon  culture— using  the  bouillon  itself  to 
soak  off  the  blood  from  the  paper. 


406  SPECIAL    PATHOLOGY    OF    THE   BLOOD. 

When  the  blood  is  collected  on  glass,  it  may  be  dissolved  by 
putting  water  on  the  glass  and  rubbing  the  dried  blood  in  it 
until  a  decided  red  tinge  is  obtained.  A  drop  of  this  mixture  is 
then  diluted  and  mixed  with  the  bouillon  culture.  Johnson 
does  not  pay  much  attention  to  the  dilution  of  the  mixture  of 
dried  blood  and  water,  before  examination,  as  he  does  not  find 
it  necessary  with  his  attenuated  cultures.  If  necessary  blood 
can  be  collected  in  wire  loops  of  a  given  size,  fairly  accurate 
dilutions  can  be  made. 

A.   The  Fluid  Serum— Quick  Method. 

The  ear  is  pricked  in  the  ordinary  way  and  about  twenty 
drops  are  forced  out  by  strong  squeezing.  The  blood  is  received 
in  a  small  (preferably  two-inch)  test-tube,  with  the  edge  of  which 
each  drop  is  scraped  off  the  ear ;  or  we  may  suck  the  blood  into 
a  capillary  pipette  and  expel  it  again  into  a  test-tube  or  other 
receptacle.  There  is  no  need  of  cleansing  the  skin  or  sterilizing 
the  test  tubes  in  this  method  of  procedure,  as  the  whole  process 
is  finished  up  so  rapidly  that  there  is  no  time  for  contaminating 
organisms  to  grow. 

The  blood  when  collected  may  be  at  once  centrifugalized, 
and  the  plasma  used  for  the  test,  or  we  may  wait  till  clotting 
occurs  and  use  the  serum.  When  blood  is  collected  in  test- 
tubes,  it  is  convenient  to  free  the  edges  of  the  clot  from  the  tube 
all  round  with  some  sharp  instrument,  so  that  the  serum  may 
not  be  pinned  down  underneath  the  clot,  as  it  often  is.  If  this 
is  done,  a  drop  of  serum  can  be  had  within  two  or  three  minutes, 
and  is  then  mixed  with  ten  drops  of  bouillon  culture,  as  above 
described,  and  examined  at  once  between  slide  and  cover-glass. 

(Dried  serum  can  be  used  in  the  same  way  as  dried  blood, 
but  has  no  special  advantages  and  has  not  been  frequently  em- 
ployed by  any  observer.) 

B.    The  Fluid  Serum— Slow  Method. 

This  was  the  way  originally  described  by  Widal,  or  rather 
applied  by  him  to  the  diagnosis  of  disease. 

The  serum  must  be  collected  asepticalty,  and  many  have 
therefore  preferred  to  take  it  from  a  vein  of  the  elbow,  which 
is  punctured  with  a  sterile  syringe,  as  described  *on  page  47. 


THE   CLUMP   REACTION.  407 

Durham  cleans  the  skin  of  the  ear  with  a  two-per-cent  solu- 
tion of  lysol,  sucks  blood  into  a  sterile  pipette,  and  blows  it  out 
again  into  a  sterile  test-tube  to  wait  for  clotting. 

Or,  if  we  desire  to  keep  and  transport  the  fluid  serum,  it  is- 
sucked  into  the  bulb  of  a  modified  Pasteur's  pipette  (sterile), 
such  as  is  shown  in  Fig.  58,  which  is  then  sealed  by  heat  at  the 
points  A  and  B.     In  this  way  the  serum  will  keep  for 
an  indefinite  period  and  can  be  sent  across  the  ocean, 
as  was  recently  done  at  the  request  of  the  New  York 
Health  Department. 

When  we  are  ready  to  use  the  serum,  one  of  the 
pointed  ends  of  the  sealed  bulb  is  broken  off  and  the 
serum  expelled  by  gently  warming  the  other  end. 

The  serum  aseptically  collected  by  one  of  the 
above-described  methods  is  then  added : 

1.  To  ten  times  its  volume  of  bouillon  culture  of 
bacilli,  i.e.,  eight  drops  to  five  cubic  centimetres  of 
culture,  in  a  test-tube,  which  is  then  left  from  eight 
to  twelve  hours  in  the  thermostat  at  37°  C. ;  or 

2.  The  serum  may  be  added  to  ten  times  its  vol- 
ume of  pure  sterile  bouillon,  and  then  a  trace  of  the 
dry   agar  culture  of  bacilli   added  with  a  platinum 
loop  and  thoroughly  mixed  with  the  bouillon  by  rub- 
bing the  loop  against  the  inside  of  the  test-tube,  which 
is  then  kept  twenty-four  hours  at  37°  C.     If  the  first 
of  these  ways  is  used,  we  get  the  effect  of  the  serum 
on  the  fully  grown  bacilli;  in  the  second  way— which 

usually  needs  fully  twenty-four  hours— it  works  on  the  nascent 
and  immature  organisms. 

Whichever  method  is  used,  we  find  that  within  from  eight 
to  twenty -four  hours  a  remarkable  change  takes  place  in  the 
appearance  of  the  culture  when  serum  from  a  case,  e.g.,  of  ty- 
phoid fever,  is  added  to  typhoid  bacilli,  nascent  or  full-grown. 
The  uniform  turbidity  of  the  bouillon  is  gone  and  the  liquid 
is  either  clear  with  an  abundant  flocculent  sediment  at  the 
bottom  of  the  tube,  or  is  filled  with  coarse  whitish  particles 
separated  from  each  other  by  clear  bouillon.  The  latter  change 
may  take  place  the  instant  the  serum  is  added  to  the  culture,  but 
usually  needs  from  six  to  eight  hours,  and  the  full  end  reaction 
is  often  not  completed  till  twenty -four  hours  elapse.  Fraenkel 


408  SPECIAL    PATHOLOGY    OF   THE    BLOOD. 

finds  the  reaction  most  marked  in  twelve  to  fourteen  hours — less 
so  in  twenty -four. 

A  control  tube  containing  the  same  proportions  of  the  same 
culture  and  of  a  healthy  person's  serum  should  always  be  put 
into  the  thermostat  along  with  the  serum  to  be  tested.  Occa- 
sionally in  such  a  control  tube  fine  but  visible  whitish  dust 
forms,  but  such  dust  usually  disappears  later  of  itself,  or  can  be 
dissolved  and  the  original  diffuse  turbidity  produced  by  shaking 
the  tube,  while  shaking  a  tube  in  which  the  true  clump  reaction 
has  taken  place  will  not  break  up  the  clumps  nor  restore  the 
original  turbidity. 

As  above  suggested,  the  microscopical  examination  of  the 
"  dust"  seen  in  such  a  test,  or  of  the  precipitate  formed  at  the 
bottom  of  the  tube,  shows  it  to  be  made  up  of  clumps  of  bacilli 
similar  to  those  seen  in  the  quick  method,  but  generally  larger. 

The  reaction  is  considerably  less  typical  when  the  serum 
used  is  dark-colored,  but  the  effects  of  shaking  the  tube  and  the 
comparison  with  the  control  usually  enable  us  to  decide. 

Some  precipitate  and  clumping  may  occur  in  cases  not 
typhoid:  (a)  when  the  bouillon  has  not  been  filtered  and  con- 
tains sediment,  in  which  the  bacilli  may  become  entangled ;  (b) 
when  a  large  amount  of  the  dry  culture  is  added  (in  trying  the 
slow  method  on  nascent  bacilli)  and  not  thoroughly  mixed  with 
the  bouillon;  (c)  in  case  the  platinum  loop  is  not  quite  cooled 
before  the  agar  culture  is  taken  upon  it ;  (d)  in  case  the  culture 
is  impure  or  the  serum  not  aseptic. 

3.  Blister  Fluid. 

Biggs  and  Park  find  the  fluid  obtained  by  blistering  the  most 
satisfactory.  A  fly -blister  the  size  of  a  five-cent  piece  is  applied, 
and  in  from  six  to  eighteen  hours  a  blister  has  formed.  The 
serum  from  the  blister  is  collected  with  a  capillary  tube,  the 
ends  of  which  are  then  sealed.  This  serum  is  admirably  clear 
and  free  from  blood  corpuscles  and  answers  the  purpose  well. 

This  method  has  never  been  extensively  used  by  other  ob- 
servers, except  Puglieri. 

Advantages  and  Disadvantages  of  the  "  Quick  Method"  and  of 
the  "Slow  Method." — In  favor  of  the  quick  method  are:  (1)  its 
quickness,  (2)  the  small  amount  of  blood  needed,  and  (3)  absence 
of  any  need  for  asepsis  and  of  any  danger  of  contamination. 


THE    CLUMP    REACTION.  409 

Against  it  are :  (a)  the  occasional  occurrence  of  pseudo-reac- 
tions or  false  clumps,  which  will  be  discussed  on  page  418;  (b) 
that  it  needs  a  microscopic  examination  instead  of  being  evident 
to  the  naked  eye,  as  in  the  slow  method ; '  (c)  that  it  needs 
watching  and  cannot  be  left  to  "go  on  of  itself." 

In  favor  of  the  slow  method  are : 

(1)  That  to  some  observers  it  appears  more  reliable  and  less 
apt  to  give  pseudo-reactions. 

(2)  That  it  can  be  seen  with  the  naked  eye. 

(3)  That  we  do  not  need  to  watch  it  but  simply  to  note  the 
results  at  the  end  of  from  eight  to  twenty-four  hours. 

Against  it  are  its  slowness,  the  danger  of  contamination,  the 
need  of  a  large  quantity  of  blood  and  of  a  thermostat." 

On  the  whole  the  great  majority  of  observers  prefer  the  quick 
method,  and  it  has  been  used  in  three-fourths  of  the  reported 
experiments.  My  own  experience  has  been  exclusively  with 
the  quick  method. 

Breuer,  Catrin,  and  Vanlair  and  Beco  are  the  only  ones  who 
distinctly  prefer  the  twenty-four-hour  method  in  all  cases. 

2.  THE  CULTURES  OF  TYPHOID  BACILLI  TO  BE  USED. 

1.  The  stock  cultures  grow  best  on  agar. 

2.  Ordinary   peptone  bouillon,   free  from  sediment,   is  the 
best  medium  for  the  test  culture.     It  should  be  just  on  the  verge 
of  litmus  acidity,  giving  no  blue  to  the  red  paper  and  requiring 
3.5  per  cent  of  normal  alkali  to  render  it  neutral   to  phenol- 
phthalein. 

3.  All  observers  agree  that  the  cultures  should  be  young — 
that  is,  that  the  transplantation  to  bouillon  should  have  taken 
place  not  more  than  from  twelve  to  twenty-four  hours  before  the 
culture  is  used.     Many  observers  find  even  the  twenty-four-hour 
culture  too  old  and  prefer  a  twelve-  to  twenty-hours-old  culture 
in  all  cases. 

4.  The  virulence  and  motility  of  the  culture  are  very  impor- 
tant.    Most  observers  agree  that  the  more  virulent  the  culture 
the  more  readily  and  characteristically  it  is  clumped  by  typhoid 
serum.     Biggs  and  Park  noticed  that  one  culture  of  peculiarly 

1  Greene  states  that  with  the  quick  method  a  mottling  of  the  specimen  can 
be  seen  with  the  naked  eye. 

?  Pick  states  that  no  thermostat  is  needed,  and  that  sedimentation  takes 
place  readily  at  room  temperature. 


410  SPECIAL    PATHOLOGY   OF    THE   BLOOD. 

great  virulence  recently  received  from  Pfeiffer  of  Berlin  worked 
much  better  in  their  cases  than  any  other  of  the  cultures 
used.  I  have  repeatedly  noticed  that  cultures  recently  taken 
from  autopsies  on  patients  who  had  died  during  the  acme  of 
the  fever  were  much  more  easily  clumped  than  those  taken  in 
autopsies  on  patients  who  had  succumbed  late,  after  the  tem- 
perature had  been  normal  for  some  time.  I  have  also  noticed 
that  virulent  cultures  grown  for  a  long  time  in  the  thermostat 
with  weekly  transplantations  gradually  lost  a  good  deal  of  their 
susceptibility  to  the  clumping  power  of  typhoid  sera. 

Presumably  these  changes  mean  a  loss  of  virulence  in  the 
culture,  especially  as  they  have  always  been  accompanied  by  a 
diminution  in  the  rapidity  of  motion  in  the  bacilli.  Cultures 
fresh  from  an  autopsy  usually  show  furious  motility,  the  bacilli 
darting  about  like  a  swarm  of  insects,  but  after  repeated  trans- 
plantations and  long  sojourn  in  the  thermostat  a  good  deal  of 
this  motility  is  gradually  lost.  Cultures  kept  at  room  tempera- 
ture preserve  their  motility  for  much  longer  periods. 

For  those  who  have  no  opportunity  to  test  the  virulence  of 
organisms  on  animals,  the  motility  is  the  best  guide  to  virulence, 
and  the  rule  should  be :  Among  the  available  cultures  select  that 
having  the  most  rapid  motility. 

4.  Certain  cultures  contain  small  clumps  of  bacilli  before  any 
serum  has  been  added  to  them.     This  is  a  very  important  point 
and  has  doubtless  misled  many.     In  consequence  of  this  possi- 
bility every  culture  must  be  examined  each  time  that  a  test  is 
made.     It  is  not  sufficient  to  examine  each  culture  once  for  all, 
as  cultures  vary  slightly  from  day  to  day  and  also  vary  in  dif- 
ferent portions  of  the  culture  tube.    For  instance,  ten  drops  taken 
from  the  middle  of  the  bouillon  may  be  found  free  from  clumps, 
while  if  the  next  ten  drops  be  taken  from  the  surface  or  from  the 
bottdm  of  the  liquid,  they  may  contain  clumps. 

This  point  has  been  strongly  insisted  on  by  Widal,  Eenon. 
and  others. 

5.  It  is  hardly  necessary  to  say  that  the  cultures  used  must 
have  been  submitted  to  all  the  regular  tests  for  the  recognition 
of  the  typhoid  bacillus,  and  that  the  greatest  care  must  be  used 
to  avoid. their  contamination. 


THE    CLUMP   REACTION.  411 

The  Use  of  Suspensions  or  Emulsions    of  the  Bacilli  instead  of 

Cultures. 

A  few  observers — particularly  Durham  and  Griiber — have 
preferred  to  use  a  mixture  of  small  bits  of  solid  agar  culture  and 
bouillon  instead  of  bouillon  cultures.  The  majority  of  writers 
prefer  cultures. 

The  Use  of  Attenuated  Cultures. 

Johnson  finds  that  with  his  methods  of  technique  (dried 
blood  and  no  definite  dilution)  pseudo-reactions  were  not  uncom- 
mon with  the  blood  of  healthy  people. 

He  avoids  this  by  using  attenuated  cultures — i.e.,  old  stock 
agar  cultures  kept  at  room  temperature  and  not  transplanted 
more  than  once  a  month,  from  which  he  planted  his  bouillon 
cultures.  This  gives  a  bacillus  of  reduced  virulence  and 
slow,  gliding  motion,  which  is  clumped  far  less  readily  than 
the  virulent  varieties.  Bouillon  cultures  of  this  kind  from  twelve 
to  twenty-four  hours  old  he  found  to  react  in  fifteen  minutes 
with  all  typhoid  sera  and  not  with  other  sera  even  after  forty- 
eight  hours'  waiting. 

Durham,  Biggs  and  Park,  and  Delepine,  on  the  contrary, 
found  such  cultures  unsatisfactory,  in  that  it  was  not  possible  to 
avoid  pseudo-reactions  with  sera  of  diseases  not  typhoid.  I 
have  been  equally  unsuccessful  with  this  method,  and  believe 
with  Biggs  and  Park  that  the  most  virulent  cultures  are  the 
most  reliable,  if  fluid  blood  or  serum  is  used.  When  dried 
blood  must  be  used,  the  attenuation  of  cultures  as  advised  by 
Johnson  is  probably  the  best  plan. 

The    Clump  Reaction  with  Dead  Bacilli. 

One  of  the  most  remarkable  and  interesting  features  of  the 
clump  reaction  is  the  possibility  of  obtaining  it  with  bacilli  that 
have  been  killed  by  heat  or  by  formol. 

Widal  observed  that  bouillon  cultures  of  typhoid  bacilli  ex- 
posed to  a  temperature  of  57°-60°  C.  for  one-half  to  three- 
quarters  of  an  hour  lost  scarcely  any  of  their  susceptibility  to 
the  clumping  action  of  typhoid  serum,  though  they  are  quite 
dead.  Higher  temperatures  (70°-120°  C.)  take  away  more 
and  more  of  the  susceptibility  to  clumping  and  also  cause 


412  SPECIAL   PATHOLOGY   OF   THE    BLOOD. 

the  formation  of  false  clumps  without  the  addition  of  any  serum 
whatever. 

Similarly  one  drop  of  ordinary  formol  mixed  with  one  hun- 
dred and  fifty  drops  of  bouillon  culture  of  Eberth's  bacilli  kills 
them,  but  apparently  "  embalms"  them,  so  that  their  suscep- 
tibility to  clumping  is  scarcely  if  at  all  lessened,  even  after  the 
lapse,  of  five  months. 

The  bacilli  gradually  sink  to  the  bottom  of  the  tube,  but 
when  shaken  up  distribute  themselves  evenly  throughout  the 
medium  and  can  be  used  like  fresh  cultures  for  diagnostic  pur- 
poses. Bordet  has  noted  the  same  thing  with  cultures  of  the 
cholera-vibrio  killed  with  chloroform. 

These  facts  seem  at  first  sight  to  conflict  with  the  statement 
made  above,  that  fresh,  motile,  and  virulent  cultures  are  best,  and 
that  old  ones  are  not  reliable.  But  it  may  be,  as  Widal  sup- 
poses, that  the  rapid  action  of  heat  or  formol  on  virulent 
cultures  preserves  unchanged  the  power  which  prolonged 
growth  in  old  media  destroys.  If  this  be  true,  it  will  enable 
us  to  dispense  with  our  thermostat  and  careful  nursing  of 
cultures,  since  a  single  first-rate  culture  can  be  thus  "em- 
balmed" and  preserved  for  use  at  all  times  and  under  all  cir- 
cumstances. 

Widal' s  results  with  this  method  have  not  yet  been  confirmed 
by  others. 

3.  DILUTION  AND  THE  TIME  LIMIT. 
I.  Dilution. 

We  have  mentioned  without  explanation  in  various  parts  of 
this  chapter  that  the  blood  serum  or  other  fluids  used  must  be 
diluted  with  at  least  ten  times  their  volume  of  bouillon  culture 
before  any  observation  is  made  as  to  their  action  on  the  bacilli 
of  typhoid  fever. 

The  reasons  for  this  dilution  and  for  the  proportions  1 : 10 
are  the  following : 

It  has  been  found,  as  mentioned  above,  that  the  mere  forma- 
tion of  clumps  in  bouillon  cultures  of  Eberth's  bacilli  is  not  a 
power  exclusively  possessed  by  typhoid  serum.  The  serum  of 
persons  suffering  from  other  diseases  and  even  of  healthy  persons 
will  form  clumps  exactly  like  those  formed  by  typhoid  bacilli, 


THE    CLUMP    REACTION.  413 

provided  it  is  not  diluted.  The  only  known  peculiarity  of  the 
typhoid  serum  is  that  its  clumping  power  is  greater  than  that  of 
other  diseases,  and  persists  in  spite  of  dilution,  while  the  sera 
of  diseases  other  than  typhoid  lose  their  power  to  clump  typhoid 
bacilli  when  diluted  ten  times  or  more. 

II.   Time  Limit. 

But  even  this  statement  must  be  further  limited.  The  sera 
of  various  other  diseases,  and  of  healthy  persons,  will  sometimes 
clump  typhoid  bacilli  even  in  a  1:10  dilution,  provided  ice  give 
them  time  enough.  We  must  therefore  limit  the  period  within 
which  a  serum  must  "  come  up  to  the  scratch"  and  do  its  work, 
if  it  is  to  bs  considered  a  typhoid  serum. 

Following  Griiber  and  Durham,  a  time  limit  of  one-half  hour 
has  been  adopted  by  Griinbaum,  Block,  Haedke,  Park,  and 
others. 

All  that  these  more  or  less  arbitrary  figures  stand  for  is  this : 
that  hitherto  no  one  has  reported  any  considerable  number  of  cases 
in  irliich  the  serum  of  any  disease  or  of  healthy  persons  has  clumped 
typhoid  bacilli  within  one-half  hour,  wlien  diluted  1:10  and  used 
with  unimpeachable  technique. 

Johnson  finds  dilution  unnecessary  with  his  methods  of  pre- 
paring the  cultures,  and  Widal  only  lately  has  admitted  the  ne- 
cessit}T  of  a  time  limit,  but  the  majority  of  careful  and  non-par- 
tisan observers  are  agreed  that  these  precautions  are  necessary 
unless  attenuated  cultures  are  used.  If  at  any  time  cases  are  re- 
ported in  which,  despite  these  precautions,  a  clumping  of  typhoid 
bacilli  has  occurred  with  non-typhoidal  sera,  it  will  be  necessary 
to  raise  the  dilution  to  1 : 15  or  1 :  20.  Indeed  there  are  many 
who  think  it  should  now  be  placed  at  one  of  these  two  figures 
or  even  higher.  Many  German  observers  prefer  to  use  a  dilu- 
tion of  1 : 40  or  1 :  50  and  a  time  limit  of  one  or  two  hours. 
This  amounts  to  about  the  same  thing  as  1 : 10  dilution  with  a 
limit  of  fifteen  minutes.  . 

The  clump  reaction  in  typhoid  fever  is  to  be  considered 
specific  and  pathognomonic  only  in  the  sense  that  it  occurs  more 
readily  and  in  presence  of  greater  dilution  in  typhoid  than  in 
any  condition  yet  reported.  (For  details  and  exceptions  on 
these  points  see  page  370.) 

The  serum  of  most  cases  of  typhoid  fever  during  the  second 


414 


SPECIAL   PATHOLOGY   OF   THE   BLOOD. 


week  will  clump  typhoid  bacilli  when  diluted  1 : 40,  and  many 
sera  preserve  the  power  even  at  1 : 100  or  higher.  Widal  has 
seen  it  as  high  as  1 : 12,000.  The  following  table  .from  Biggs 
and  Park  illustrates  these  points  well : 


Q 

History,  symptoms,  and 
diagnosis  at  time  of  taking 
blood  specimens. 

Corrected 
diagnosis  on 
completion 
of  illness. 

Reaction  of  bacilli 
in  broth  cultures  to 
serum  in  different 
dilutions. 

Reaction. 

Amount 
of 
serum. 

Amount 
broth 
culture. 

1 

Adult;  sick  four  weeks,  con- 
tinuous high  fever;  pleurisy  ; 
"  tuberculosis  "  with  possi- 
bility of  typhoid. 

Tuberculosis. 

1 

1 

Not  appreciable. 

2 

Boy;  sick  two  weeks;  con- 
tinued moderate  fever,  abat- 
ing when  test  was  made; 
prostration,  constipation  ;  no 
typhoid  symptoms  except 
fever  and  prostration; 
"atypical  typhoid  fever." 

Uncertain. 

1 

1 

Not  appreciable. 

3 

Adult;  symptoms  of  acute 
articular  rheumatism  only; 
"  acute  articular  rheuma- 
tism." 

Acute   rheu- 
matism. 

1 
1 
1 

1 
4 
9 

Delayed  moderate. 
Delayed  very  slight. 
Not  appreciable. 

4 

Adult;  just  convalescent  after 
sickness  giving  character- 
istic symptoms  and  physical 
signs  of  pneumonia;  "  pneu- 
monia." 

Pneumonia. 

1 
1 
1 
1 

1 

4 
9 
19 

Immediate  marked. 
Delayed  moderate. 
Delayed  slight. 
Not  appreciable. 

ft 

Adult;  continued  high  fever; 
enlarged  spleen;  typhoid 
bacilli  obtained  from  spleen; 
"typhoid  fever." 

Typhoid 
fever. 

] 
1 

1 

1 
4 
9 

Immediate. 
Delayed  incomplete. 
Delayed  very  slight. 

6 

Adult;  relapse  after  four 
weeks  of  continuous  fever 
with  typhoid  symptoms; 
"relapse  after  typhoid  fever" 

Typhoid 
fever. 

1 
1 
1 
1 
1 

1 
10 
50 
100 
200 

Marked  immediate. 
Marked  immediate. 
Marked  immediate. 
Delayed  moderate. 
Dela}'ed  slight. 

7 

Adult;  seven  days  continued 
high  fever;  typhoid  symp- 
toms; two  days  later  an 
atypical  rash  ;  "typhoid 
fever." 

Typhoid 
fever. 

1 
1 
1 
1 
1 

1 
9 
49 
99 
199 

Marked  immediate. 
Mai-ked  immediate. 
Marked  immediate. 
Delayed  but  marked. 
Delayed  moderate. 

The  Microscopic  Examination. 

An  artificial  light  is  preferable.  The  use  of  hanging-drop 
preparations  is  unnecessary,  as  a  simple  slide  and  cover-glass  is 
satisfactory.  A  hanging-drop  cell  may  be  extemporized  by 
cementing  with  marine  glue  a  small  brass  curtain  ring  to  a  slide, 
and  inverting  the  cover-glass  within  it,  as  advised  by  Stokes. 


THE   CLUMP   REACTION.  415 


SEED-DIAGNOSIS  or  TYPHOID. 

I  have  collected  over  3,000  cases  of  supposed  typhoid  fever 
in  which  the  clump  reaction  was  tested  as  above  described  either 
with  the  fluid  or  dried  blood.  Of  these,  95  per  cent  showed  a 
serum  reaction  at  some  time  in  their  course;  2,500  odd  controls 
showed  about  2  per  cent  of  positive  results  in  cases  other  than 
typhoid.  Altogether  then  about  5,500  cases  have  been  tested. 
If  we  leave  out  the  reports  of  those  whose  experience  covers  less 
than  100  cases,  we  have  left  4,339  cases  observed  by  18  physi- 
cians in  which  the  percentage  of  error  is  2  per  cent  only. 

There  seems  to  me  no  doubt  of  the  fact  that  the  serum  reac- 
tion is  present  in  some  part  of  the  course  of  95  or  more  per 
cent  of  all  cases  of  typhoid  fever,  and  absent  in  95  or  more 
per  cent  of  all  other  conditions.  But  it  is  also  true  that  it 
is  absent  in  some  part  of  the  course  of  many  cases  of  typhoid 
—usually  in  the  earliest  or  latest  days  of  the  fever — and 
this  fact  makes  it  necessary  to  retest  every  case  in  which  a 
negative  result  has  been  found,  and  even  in  some  cases  to  make 
a  considerable  number  of  tests  before  a  positive  result  is  ob- 
tained. My  own  experience  covers  202  cases  of  ty  phoid,  all  but 
7  of  which  were  positive,  and  in  4  of  these  there  was  no  op- 
portunity of  retesting.  In  the  last  108  cases,  all  of  which  were 
carefully  retested,  there  has  not  been  a  single  failure,  though  in 
some  the  reaction  was  very  late.  Out  of  376  controls  one  re- 
acted like  typhoid,  a  case  of  pernicious  anaemia  in  a  negro. 

Hoiv  early  does  the  reaction  appear  ? 

Few  of  the  many  observers  who  have  written  on  this  point 
have  discussed  how  the  beginning  of  the  disease  is  settled  and 
what  they  mean,  e.g.,  by  the  "fifth  day  of  the  disease."  It 
might  be  dated  from  the  first  day  of  malaise  arid  indisposition, 
from  the  nose-bleed  or  the  beginning  of  headache,  or  from  the 
time  of  going  to  bed. 

Allowing  for  such  serious  uncertainties  as  this,  we  find  that 
while  the  majority  of  observers  record  the  sixth  to  eighth  day 
as  the  earliest  on  which  the  reaction  appears,  there  are  quite  a 
number  of  cases  mentioned  in  which  it  was  seen  on  the  fourth  or 
fifth  day ;  a  few  record  reactions  present  on  the  third  day,  and 
two  or  three  on  the  second  dav. 


416  SPECIAL    PATHOLOGY    OF    THE   BLOOD. 

As  above  mentioned,  we  have  no  way  of  knowing  what  the 
"second  day"  means  in  these  cases. 

In  my  own  observations  I  have  called  the  first  day  in  bed  the 
first  day  of  the  disease  (though  I  am  aware  that  many  patients 
are  sick  some  time  before  taking  to  bed),  because  it  was  the  only 
date  that  could  be  definitely  fixed  in  all  cases.  With  this 
nomenclature  I  have  found  the  reaction  present  on  the  first  day 
in  two  cases  and  on  the  second  in  three  cases. 

Counting  from  the  first  day  on  which  the  patient  felt  sick  in 
any  way,  the  fifth  day  is  the  earliest  reaction  day  in  my  series. 
In  these  figures  we  have  always  to  remember  that  in  no  case  was 
the  blood  tested  at  all  previous  to  the  day  on  which  the  positive 
test  occurred,  so  that  their  meaning  is:  In  some  cases  (what 
proportion  of  all  is  unknown)  the  serum  reaction  occurs  at  least  as 
soon  as  the  fifth  day  of  malaise  or  the  first  day  in  bed,  andperlui/^ 
sooner.  Not  infrequently  the  reaction  antedates  the  appearance 
of  rose  spots,  splenic  enlargement,  or  the  diazo  reaction  by 
several  days.  On  the  other  hand,  I  have  known  the  bacilli 
to  be  isolated  from  the  stools  before  the  serum  reaction  ap- 
peared; but  this  is  rare. 

Experiments  on  animals  show  that  the  clump  reaction  ap- 
pears in  the  blood  on  the  third  to  eighth  day  after  inoculation 
with  dead  typhoid  bacilli. 

How  late  in  the  disease  does  the  reaction  last  ?  The  majority 
of  observations  agree  that  in  mild  cases  the  reaction  may  die  out 
even  before  the  end  of  the  fever.  On  the  other  hand,  the  re- 
action usually  lasts  several  months,  and  Widal  found  it  still 
present  after  one  year  in  3  out  of  22  cases  in  which  he  tried  it. 
These  3  subjects  had  had  very  severe  cases  of  typhoid  three, 
seven,  and  nine  years  previously.  It  has  been  reported  present 
twenty  and  even  thirty  years  after  the  fever.  Biggs  and  Park 
found  the  reaction  more  constant  in  the  fourth  week  than  at 
any  other  time — 76  per  cent  of  their  cases  tested  between  the 
thirtieth  and  sixtieth  days  still  showed  the  reaction,  and  5  of 
8  cases  still  reacted  after  three  to  four  months. 

The  reaction  almost  always  persists  in  relapses,  even  to  a 
second  or  third  relapse,  and  occasionally  it  is  present  only  in 
relapse  and  not  in  the  original  attack  at  all.  Biggs  and  Park 
record  a  case  in  which  the  diagnosis  was  proved  during  the 
original  attack  by  puncture  of  the  spleen,  which  showed  a  pure 


THE   CLUMP   REACTION.  417 

culture  of  Eberth's  bacilli,  yet  no  serum  reaction  was  present 
until  the  second  day  of  the  relapse.  I  have  observed  several 
similar  cases,  and  quite  frequently  not  found  the  reaction  until 
convalescence.  The  failure  to  follow  up  such  cases  as  these 
accounts  for  many  negative  reports.  In  one  of  Elsberg's  cases 
the  total  duration  of  the  clumping  power  in  the  blood  was  only 
eight  days ;  in  another  only  twelve  days. 

The  continuance  of  the  reaction  after  the  fall  of  the  tempera- 
ture is  no  indication  (as  some  have  supposed)  that  relapse  is 
coming,  for  in  many  such  cases  no  relapse  follows.  Very  fre- 
quently the  reaction  is  absent  on  a  given  day  though  present 
the  day  before  and  after. 

I 
The  Intensity  of  the  Reaction. 

Widal  and  others  have  studied  the  intensity  of  the  reaction 
at  different  periods  of  the  disease,  judging  by  the  amount  of 
dilution  which  could  be  practised  without  destroying  the  power 
of  a  given  serum. 

Examples  of  this  have  already  been  given  in  the  table  on  page 
363.  The  majority  of  typhoids  in  the  second  and  third  week 
yield  serum  which  will  clump  Eberth's  bacilli  when  diluted  1 : 40 
and  many  cases  will  do  so  even  at  1 : 100.  Strangely  enough, 
some  typhoid  sera  clump  better  when  diluted  1 : 16  or  more 
than  when  undiluted.  This  has  been  repeatedly  noted  by 
Grunbaum. 

Widal  and  Sicard  record  clamping  with  a  dilution  of  1 : 12,000 
and  1:1,800  and  consider  that  in  the  active  stages  of  the  dis- 
ease a  dilution  of  1 : 60  or  1 :  80  does  not  usually  present  the  re- 
action, while  in  convalescence  the  power  of  the  serum  falls  off 
gradually  and  is  not  always  present  even  at  1 : 10. 

Biggs  and  Park  find  one-half  their  typhoid  cases  furnish 
serum  with  the  power  to  clump  in  1 :  40  dilution  by  the  end  of 
the  first  week,  and  have  occasionally  noted  the  reaction  even 
with  a  dilution  of  1 : 200. 

Jemma  found  the  reaction  most  intense  at  the  acme  of  the 
fever  and  greater  during  the  evening  exacerbation  of  fever  than 
in  the  morning. 
27 


418  SPECIAL  PATHOLOGY  OF  THE  BLOOD. 

EFFECTS  OF  THE  SERA  OF  OTHER  DISEASES. 

Negative  results  are  reported  in  the  following  list  of  diseases 
experimented  on  as  controls :  Pneumonia,  typhus,  Malta  fever, 
tuberculosis  in  its  various  forms,  including  miliary  tuberculo- 
sis, tubercular  meningitis,  pneumococcus  meningitis  (purulent) 
and  epidemic  cerebro-spinal  meningitis,  diphtheria,  influenza, 
ulcerative  endocarditis,  erysipelas,  puerperal  septicaemia,  gonor- 
rhceal  septicaemia,  measles  and  scarlet  fever,  tonsilitis,  acute 
articular  rheumatism,  malaria,  leprosy,  syphilis,  bronchitis, 
pleurisy  with  effusion,  acute  and  chronic  nephritis,  mumps,  oti- 
tis  media,  catarrhal  jaundice,  sciatica,  acromegalia,  hysterical 
vomiting,  Graves'  disease,  gangrene  of  the  lung,  appendicitis, 
abscess  and  cirrhosis  of  the  liver,  acute  febrile  gastro-enteritis 
("  embarras  gastrique"),  cancer  of  the  various  organs,  alveolar 
abscess  with  fever,  osteomyelitis,  bubo  with  fever,  arthritis  de- 
formans,  chronic  laryngitis,  intestinal  obstruction,  general  peri- 
tonitis, leukaemia,  Hodgkin's  disease,  pernicious  anaemia,  diar- 
rhoea, chronic  gastritis,  gallstone  colic  with  fever,  dysentery, 
acute  mania,  stuporous  melancholia,  synovitis,  neurasthenia, 
varicose  veins,  orchitis,  suppurative  thyroiditis,  perinephritis, 
cystitis,  pericarditis,  empyema,  brain  abscess,  valvular  heart 
disease,  diabetes,  gas  poisoning,  alcoholism,  and  eclampsia. 

The  important  diseases  of  this  list,  such  as  pneumonia, 
tuberculosis,  meningitis,  and  typhus,  have  been  tried  many 
times.  Biggs  and  Park  got  a  positive  result  in  one  case  said 
to  be  typhus.  There  is  a  chance  of  mistaken  diagnosis  here. 

Positive  Results  of  the  Sera  of  Other  Diseases   ivith    Typhoid 

Bacilli. 

Many  of  the  supposed  contradictions  of  the  law,  that  the 
typhoid  bacilli  are  clumped  within  one-half  hour  only  by  typhoid 
serum  when  a  dilution  of  one  part  of  serum  to  ten  or  more  of  culture 
is  used,  are  due  to  faulty  technique.  Such  are  probably  the  cases 
reported  by  Ferrand  and  Theoari  (septicaemia),  Villies  and 
Battle  (malaria),  Gehrmann  and  Wynkoop  (pneumonia,  bron- 
chitis, pleurisy),  and  Stern  (otitis  media). 

On  the  other  hand  there  are  a  few  cases  reported  by  careful 
observers  in  which  a  genuine  clumping  of  typhoid  bacilli  has 
been  caused  by  the  sera  of  other  diseases,  viz. :  Pernicious 


THE    CLUMP   REACTION.  419 

malaria,  comatose,  one  case  (Block) ;  diabetic  coma,  one  case 
(Block) ;  jaundice,  one  case  (Catrin) ;  tubercular  meningitis,  one 
case  (Jez),  and  a  few  more. 

A  case  of  malaria,  reported  by  Catrin,  with  positive  reaction 
of  the  serum  on  typhoid  bacilli,  was  in  a  subject  who  had  had 
typhoid  five  years  before.  In  view  of  Widal's  and  Fraenkel's 
results,  this  cannot  be  counted  an  exception  to  the  general  law. 
The  same  is  true  of  Griinbaum's  much-quoted  cases,  which  he 
reported  not  as  exceptions  but  to  emphasize  the  necessity  of 
proper  dilution.  Using  a  proportion  of  1:1  instead  of  1 : 10,  he 
got  clumping  of  typhoid  bacilli  with  the  sera  of  jaundice  (two 
cases),  meningitis  and  bronchitis  (one  case  each). 

The  cases  reported  by  Johnson,  Brannan,  Thomas,  Heed, 
and  other  observers,  in  which  the  dried  blood  of  healthy  per- 
sons and  persons  with  various  diseases  other  than  typhoid  has 
clumped  typhoid  bacilli,  are  probably  owing  to  the  uncertain- 
ties connected  with  that  method  of  procedure. 

In  most  cases  in  which  the  fluid  serum  was  also  tried  it  gave 
no  reaction. 

The  discovery  that  the  bacillus  of  psittacosis  and  the  "  bacillus 
enteritidis"  of  Gartner  are  somewhat  sensitive  to  the  action  of 
typhoid  serum  (see  page  421)  has  led  to  the  fear  that  infec- 
tions due  to  those  bacilli  might  be  mistaken  for  typhoid,  but 
this  is  wholly  an  assumption,  as  in  the  few  cases  of  these  infec- 
tions which  have  been  studied  the  serum  has  not  affected  typhoid 
bacilli. 

Further,  it  is  only  by  a  concentrated  artificial  typhoid  serum 
that  the  bacillus  of  Gartner  is  clumped,  and  the  clumping  of  the 
psittacosis  bacillus  is  quite  different  from  that  of  the  typhoid 
bacillus,  the  clumps  of  the  former  being  very  small  and  few; 
with  the  twenty-four-hour  method  no  precipitate  forms. 

Summary  of  Negative  Results. 

Out  of  over  three  thousand  cases  of  various  diseases  not  ty- 
phoid, not  over  a  dozen  have  been  proved  to  clump  typhoid  ba- 
cilli with  proper  technique.  It  is  quite  possible  that  further  im- 
provements in  technique  may  enable  us  to  prevent  even  this  very 
small  error. 


420  SPECIAL  PATHOLOGY  OF  THE  BLOOD. 

EFFECTS  OF  TYPHOID  SEBUM  ON  OTHER  BACILLI. 
(a)   On  the  Bacillus  Coli  Communis. 

Any  blood  serum  mixed  1 : 10  with  a  bouillon  culture  of  colon 
bacilli  may  cause  the  formation  of  small  clumps  without  consid- 
erable loss  of  motility.  The  effect  of  typhoid  serum  does  not 
differ  from  that  of  other  sera,  and  the  clumps  which  it  forms  are 
much  smaller  and  looser  than  those  seen  in  the  typical  typhoid 
clump  reaction.  Different  cultures  of  colon  bacilli  differ  a  good 
deal  in  their  susceptibility  to  typhoid  serum,  and  Vanlair  and 
Beco  consider  that  no  difference  can  be  made  out  in  certain  cases 
between  its  effects  on  typhoid  bacilli  or  on  colon  bacilli.  The 
majority  of  observers,  however,  find  a  decided  difference,  espe- 
cially with  the  twenty-four-hour  method.  Undiluted  typhoid 
serum  acts  more  strongly  on  colon  than  on  typhoid  bacilli,  ac- 
cording to  Grunbaum. 

Biggs  and  Park  found  that  "  a  number  of  varieties  of  motile 
bacilli  other  than  typhoid  bacilli  are  clumped  by  the  serum  of 
persons  suffering  from  typhoid  fever,  even  when  the  serum  is 
used  in  quite  high  dilutions." 

Eodet  noted  that  only  a  very  slight  effect  is  produced  by  ty- 
phoid serum  on  colon  bacilli  until  a  dilution  of  one  part  of  serum 
to  two  of  culture  is  reached. 

Fraenkel  tested  a  largo  number  of  colon  cultures  without 
getting  any  decided  effect  from  the  addition  of  typhoid  serum. 

Courmont  found  that  some  cultures  of  the  colon  bacillus  are 
clumped  by  typhoid  serum. 

Widal  saw  no  difference  between  the  effect  of  typhoid  serum 
and  that  of  other  sera  on  colon  bacilli,  but  Vedel  thinks  that 
young  cultures  are  better  clumped  by  typhoid  serum  than  by 
other  sera. 

Johnson,  who  studied  a  large  number  of  cases,  says :  "  A 
complete  colon  reaction  we  have  found  to  be  exceptional  in  or- 
dinary typhoid,  and  its  presence  would  indicate  a  condition  of 
coli  intoxication, "  which  may  be  held  to  sum  up  the  discussion 
up  to  the  present  time. 

(b)  On  the  Bacillus  Enteritidis  (Gartner). 

Griiber  and  Durham,  using  powerful  artificial  sera  from 
animals  immunized  against  Eberth's  bacillus,  were  able  to  obtain 


THE   CLUMP   REACTION.  421 

a  clumping  of  Gartner's  organisms.     No  experiments  with  hu- 
man serum  are  recorded. 

(c)   On  the  Bacillus  of  Psittacosis. 

Psittacosis  is  a  disease  affecting  parrots  and  occasionally 
transferred  by  them  to  human  beings.  A  bacillus  has  been 
found  by  Nocard  in  the  marrow  of  the  parrot's  wing-bones  which 
is  considered  the  cause.  Typhoid  serum  has  an  effect  on 
bouillon  cultures  of  this  bacillus,  which  is  to  be  distinguished 
quantitatively  from  the  clumping  of  typhoid  bacilli  by  typhoid 
serum;  the  heaps  of  psittacosis  bacilli  are  much  fewer  and 
smaller,  and  in  the  twenty-four-hour  method  the  turbidity  of  the 
cultures  does  not  disappear. 

(d)  The  Klebs-Loeffler  Bacillus  and  Pus  Cocci. 

Courmont  finds  that  typhoid  serum  clumps  Klebs-Loeffler 
bacilli  and  staphylococci,  but  is  without  effect  on  the  strepto- 
coccus and  the  bacillus  pyocyaneus. 

Summary  of  Clinical    Evidence  on  the  Sero-Diagnosis  of 
Typhoid  Fever. 

The  blood  of  over  ninety-five  per  cent  of  all  cases  of  typhoid 
shows  a  clumping  power  in  some  part  of  their  course,  but  in  at 
least  half  the  cases  this  does  not  appear  until  the  second  week 
of  the  disease,  while  in  a  small  number  of  cases  it  first  appears 
in  relapse  or  convalescence.  The  clumping  power  may  disap- 
pear before  the  defervescence  and  may  be  present  only  eight 
days  in  all ;  as  a  rule  it  persists  from  the  sixth  or  eighth  day 
until  convalescence  is  established. 

In  diseases  other  than  typhoid  a  clump  reaction  is  very 
rarely  to  be  obtained,  provided  a  dilution  of  at  least  1 : 10  is 
used  with  a  time  limit  of  one-half  hour.  There  is  no  one  dis- 
ease in  which  clumping  is  especially  apt  to  occur. 

Clinically  the  reaction  is  of  considerable  value,  especially 
when  the  diagnosis  is  in  doubt  after  the  first  week  of  the  dis- 
ease. 


422  SPECIAL   PATHOLOGY    OF   THE   BLOOD. 

SERO-DIAGNOSIS  OF  DISEASES  OTHER  THAN  TYPHOID. 
1.    Cholera. 

Griiber  and  Durham  first  showed  that  human  cholera  serum 
would  clump  cholera  vibrios,  following  the  researches  of  Pfeiffer 
in  vivo  by  demonstrating  a  similar  reaction  in  vitro. 

Achard  and  Bensaude  have  applied  this  to  the  actual  diag- 
nosis of  cholera  in  man  with  considerable  success.  In  fourteen 
cases,  thirteen  clumped  readily ;  two  of  these  were  on  the  first 
day  of  the  disease.  Thirty  control  cases  were  negative.  The 
presence  of  the  pellicle  renders  it  unsafe  to  use  bouillon  cultures 
except  such  as  have  no  pellicle,  for  bits  of  it  are  much  like 
true  clumps.  Suspensions  of  twenty-hour  gelatin  cultures  are 
more  convenient.  The  dilution  and  time  limit  are  the  same  as 
in  typhoid.  Some  cases  will  react  even  in  1 : 120  dilution. 
The  reaction  can  be  performed  with  dried  blood  and  persists 
into  convalescence  (seven  months  or  more). 

2.  Pyocyaneus  Infections. 

The  bacillus  pyocyaneus  has  been  shown  to  be  in  all  proba- 
bility the  cause  of  certain  cases  of  dysentery,  broncho-pneu- 
monia, otitis  media,  nephritis,  pericarditis,  cystitis,  and  of  a 
hemorrhagic  septicaemia  with  enteritis  in  the  new-born. 

Roger  and  Charin  found  in  1889  that  the  bacillus  pyocyaneus 
is  serum  of  animals  immunized  against  this  bacillus.  Durham 
repeated  these  observations  in  1895  and  confirmed  them. 

Here  we  have  the  clinical  infection  and  laboratory  clump- 
reaction  experiments,  but  so  far  as  I  am  aware  no  one  has  yet 
brought  the  two  together  or  tried  the  serum  of  patients  with 
pyocyaneus  infections  on  cultures  of  the  bacillus. 

3.  Diphtheria. 

Widal  reports  no  success  in  attempts  at  the  sero-diagnosis 
of  diphtheria,  and  Fraenkel  has  not  been  more  successful. 
Nicolas  and  Charrin  found  that,  although  no  true  serum  reaction 
could  be  obtained  in  diphtheria  previous  to  antitoxin  treatment, 
the  injection  of  antitoxin  produces  in  the  patient's  serum  a  de- 
cided clumping  power  over  the  Klebs-Loeffler  bacilli  within 
twenty-four  hours  of  the  time  of  injection.  This  is  especially 
marked  in  the  twenty-four-hour  method,  using  the  nascent  bacilli, 


THE    CLUMP   REACTION.  423 

as  described  on  page  407.  The  serum  retains  its  clumping  power 
for  about  two  weeks  after  the  injection  of  antitoxin,  and  then 
gradually  loses  it.  Outside  the  body  the  diphtheria  antitoxin 
easily  clumps  Klebs-Loeffler  bacilli. 

4.  Pneumococcus  Infections. 

Washburn  in  1895  noticed  that  pneumococci,  when  mixed  with 
artificial  antipneumococcus  serum  and  left  twenty-four  hours  at 
37°C,  were  clumped  in  masses  at  the  bottom  of  the  tube,  leaving 
the  upper  portions  of  the  liquid  clear.  In  other  words  he  got  a 
typical  twenty-four-hour  clump  reaction,  using  a  powerful  arti- 
ficial serum.  The  same  fact  had  previously  been  observed  by 
Metchnikoff  in  1891  and  by  Issaef  in  1892,  and  has  been  recently 
confirmed  by  Mosny. 

Widal  has  been  entirely  unsuccessful  in  finding  any  clump- 
ing with  the  serum  of  pneumonia  patients,  and  Block  finds  the 
lumping  of  pneumococci  very  slow  and  unsatisfactory.      Be- 
zancon  and  Griffon  get  similar  results. 

£.   Colon-Bacillus  Infections. 

In  view  of  the  frequent  association  of  this  bacillus  with  dis- 
ease, especially  with  the  cystitis  of  young  girls,  it  is  important 
that  the  possibility  of  a  sero-diagnosis  of  colon-bacillus  infec- 
tions should  be  studied,  but  as  yet  very  little  has  been  done  in 
this  direction. 

Griiber  and  Durham  showed  that  serum  from  animals  arti- 
ficially immunized  against  the  colon  bacillus  would  clump  that 
bacillus  strongly,  but  Widal' s  early  experiments  with  supposed 
cases  of  colon-bacillus  infection  did  not  show  any  decided  reac- 
tion, nor  did  the  serum  of  typhoids  which  showed  post-mortem 
a  secondary  colon-bacillus  infection  react  during  life  on  cul- 
tures of  this  bacillus. 

Widal  has  lately  claimed  that  in  any  case  of  colon  infection 
only  the  particular  race  of  bacilli  which  are  actually  causing  the 
case  in  question  can  be  specifically  clumped  by  the  serum  of 
that  case.  In  a  case  in  which  he  first  isolated  the  bacillus  and 
then  used  it  with  the  patient's  serum  he  got  a  clumping  as  high 
as  1 : 1,000  dilution.  Lesage  in  an  epidemic  of  infants'  diarrhoea 
found  that  the  serum  of  40  out  of  50  cases  clumped  the  colon 


424  SPECIAL   PATHOLOGY   OF   THE  BLOOD. 

bacillus  isolated  from  the  stools.  Each  of  the  40  sera  clumped 
each  of  the  40  cultures  isolated  from  the  40  cases.  The  colon 
bacillus  of  the  normal  intestine  of  infants  of  the  same  age  was 
not  at  all  affected  by  the  serum  of  the  sick  children,  nor  did  the 
serum  of  normal  infants  clump  the  organisms  from  the  infected 
children.  This  tends  to  confirm  Widal's  assertion.  Appar- 
ently this  epidemic  was  due  to  a  single  bacillus  which  could  be 
easily  isolated  and  used  for  experiment.  The  difficulty  of  iso- 
lating the  bacillus  of  every  case  that  is  to  be  tested  renders  the 
method  of  very  limited  clinical  value. 

6.  Malta  Fever. 

Wright  and  Smith  tested  the  serum  of  15  cases  of  Malta 
fever  with  the  micrococcus  melitensis  of  Bruce,  and  found  a  strong 
clump  reaction  to  occur  (1:50  in  most  cases).  On  the  typhoid 
bacillus  the  serum  of  these  cases  had  no  action.  Sixteen  cases 
of  typhoid  showed  no  reaction  with  Bruce' s  organism.  The 
evidence  in  favor  of  this  organism  as  the  cause  of  Malta  fever  is 
strengthened  by  these  facts. 

7.  Peripneumonia  of  Cattle  and  Hog  Cholera. 

Arloing  finds  that  the  serum  and  other  body  fluids  of  cattle 
suffering  from  peripneumonia  have  a  marked  clumping  power  on 
the  pneumobacillus  bovis. 

Dawson  has  had  similar  positive  results  working  with  the 
bacillus  of  hog  cholera.  Hog-cholera  serum  had  no  effect  on 
the  typhoid  or  colon  bacillus. 

8.  Proteus  Infections. 

Infections  with  the  proteus  vulgaris  or  proteus  mirabilis 
have  been  considered  causative  in  cases  of  mastoid  abscess, 
meningitis,  and  Potts'  disease.  When  found  by  culture  at 
autopsies  the  question  often  arises  whether  they  have  wandered 
in  after  or  at  the  time  of  death,  or  whether  they  were  really  con- 
cerned in  the  etiology  of  the  case.  The  investigations  of  Achard 
and  Lannelongue  appear  to  give  us  the  means  of  answering  this 
question.  They  found  that  cultures  of  the  two  species  of  pro- 
teus above  mentioned  were  markedly  clumped  by  the  serum  of 
animals  rendered  immune  to  them  by  inoculations.  This  power 


THE   CLUMP   REACTION.  425 

persists  after  death  and  even  in  putrefaction,  and  if  present  at 
any  given  autopsy  proves  that  the  infection  did  not  take  place 
during  the  last  two  days  of  life,  since  it  takes  at  least  three  days 
to  bring  the  clumping  power  into  the  serum  by  artificial  inocu- 
lation. 

9.   Oidium  Albicans. 

Roger  showed  that  the  oidium  was  well  clumped  by  the 
serum  of  animals  immunized  against  it,  and  these  observations 
have  been  confirmed  by  Charrin  and  Ostrowsky.  No  experi- 
ments with  human  thrush  have  as  yet  been  reported. 

10.   The  Bubonic  Plague. 

Zabolotny  1  studied  forty  cases  at  Bombay  in  April,  1897,  and 
found  the  reaction  absent  in  the  first  week,  present  in  1 : 10  dilu- 
tion in  the  second  week,  and  in  1 : 50  dilution  in  the  third  or 
fourth  week.  He  noted  that  the  action  of  the  infected  serum 
seemed  to  deprive  the  bacilli  of  their  capsules.  In  an  editorial 
in  the  Arch.  Busses  de  Pathologie,  May  31st,  1897,  it  is  stated  that 
the  reaction  increases  in  intensity  until  the  fourth  week  of  the 
disease  and  then  declines ;  also  that  it  is  most  marked  in  the 
severest  cases.  Feindel  (loc.  cit.)  states  that  in  the  acute  pneu- 
monic cases  the  reaction  is  absent. 

11.    Yellow  Fever. 

Sanarelli 2  states  that  the  organism  which  bears  his  name  is 
clumped  very  strongly  and  speedily  by  the  serum  of  dogs  im- 
munized against  his  bacillus.  By  normal  human  serum  it  is  not 
clumped  at  all.  By  patients  with  yellow  fever  it  clumped  very 
slowly.  Post  mortem  the  serum  clumps  more  readily  but  very 
variably.  Pothier's 3  experience  in  the  recent  New  Orleans  epi- 
demic has  been  similar. 

12.  Eelapsing  Fever. 

(a)  Diagnosis. — In  countries  where  this  disease  is  common 
the  difficulty  of  diagnosing  cases  between  attacks  (when  the. 

'Deut.  med.  Woch.,  1897,  p.  392. 

2  Annales  de  1' Institute  Pasteur,  October  27th,  1897. 

3  Personal  letter. 


426  SPECIAL   PATHOLOGY   OF   THE   BLOOD. 

spirochsetes  are  absent  from  the  blood)  is  frequently  met  with. 
Lowenthal  has  perfected  a  method  by  which  in  most  cases  the 
diagnosis  can  be  made  by  means  of  the  effect  of  the  serum  of 
suspected  cases  on  the  spirochsetes  of  other  active  cases.  The 
organism  cannot  be  cultivated  as  yet,  so  that  a  diagnosis  of 
this  kind  is  possible  only  during  epidemics  when  fresh  blood 
containing  the  organism  can  be  obtained.  A  drop  of  blood  from 
the  suspected  case  is  mixed  with  a  drop  from  a  patient  then 
undergoing  a  paroxysm,  and  the  two  are  sealed  with  wax  be- 
tween slide  and  cover-glass  and  left  in  the  thermostat  for  half 
an  hour  together  with  a  mixture  of  normal  blood  and  blood  con- 
taining spirochsetes  as  a  control.  At  the  end  of  that  time,  if 
the  case  be  one  of  relapsing  fever,  the  organisms  in  contact  with 
the  blood  from  that  case  cease  their  motion,  while  those  in  the 
control  are  lively.  It  is  not  a  clump  reaction  but  a  direct  bac- 
tericidal effect  which  persists  in  the  serum  nearly  up  to  the  time 
of  the  next  attack.  The  diagnosis  so  made  by  Lowenthal  in 
forty  cases  was  verified  in  every  case  by  the  course  of  the  dis- 
ease. In  this  way  mild  or  abortive  cases  with  few  organisms  in 
the  blood  can  also  be  identified. 

(6)  Prognosis. — If  the  above  bactericidal  power  lasts  as  late  as 
the  seventh  day  from  the  last  attack,  and  in  sufficient  intensity 
to  immobilize  the  spirochsetes  in  one  hour  or  less,  there  will  be 
no  relapse.  If  these  conditions  are  not  fulfilled  relapse  is  sure 
to  follow  unless  prevented  by  treatment.  Lowenthal  has  veri- 
fied this  prognostic  use  of  the  serum  in  over  one  hundred  cases. 

13.  Miscellaneous  Reports  on  Other  Infections. 

(a)  Griinbaum  (Lancet,  February  13th,   1897)  states  that  a 
"non-motile    diplococcus"   from   a  case  of   scarlet  fever  was 
clumped  by  the  serum  of  another  case  of  scarlet  fever. 

(&)  Delepine  (Medical  Chronicle,  October,  1896)  refers  to  suc- 
cessful experiments  with  the  tetanus  bacilli — its  antitoxin  hav- 
ing a  decided  clumping  action  upon  it.  The  serum  of  normal 
horses  clumps  the  tetanus  bacillus  to  some  extent  and  that  of 
tetanized  horses  clumps  it  intensely.  In  eight  cases  referred 
to  by  Feindel '  the  bacillus  was  clumped  by  the  serum  of  human 
tetanus. 

1  Arch.  Gen.  d.  Medecine,  October,  1897. 


THE   CLUMP  REACTION.  427 

(c)  Durham  (Lancet,  loc.  cit.)  speaks  of  the  present  antistrep- 
tococcus  serum  (Marrnorek's)  as  having  strong  clumping  power 
on  streptococci,  but  Masino  '  finds  very  few  cultures  react  to  it. 

(d)  Gilbert  and  Fournier  (Compt.  rend,  de  la  soc.  de  biol., 
December  25th,  1896)  mention  two  cases  of  human  psittacosis 
whose  serum  clumped  well  the  bacilli  obtained  from  another 
human  case  as  well  as  those  taken  from  parrots.     Clumping 
was  present  on  the  fourth  and  fifteenth  days  respectively. 

SEBO-PROGNOSIS. 

It  is  agreed  by  all  observers  that  in  a  very  general  way  severe 
cases  have  more  marked  reactions  than  mild  ones,  but  beyond 
this,  in  the  opinion  of  the  best  judges,  we  cannot  yet  go. 

Widal,  Fraenkel,  Biggs  and  Park,  and  Johnson  have  at- 
tempted no  sero-prognosis,  and  my  own  observations  are  en- 
tirely in  accord  with  this.  The  reaction  may  be  strong  in  mild 
cases  and  feeble  or  absent  in  fatal  ones. 

Certain  writers,  however,  especially  Breuer,  Courmont, 
Catrin,  and  Ullmann  and  Wohnerfc,  have  thought  the  reaction 
of  prognostic  value,  an  intense  and  early  reaction  seeming  to 
them  of  evil  omen.  Further  evidence  on  this  point  is  much 
needed. 

[For  bibliography,  see  page  429]. 

1  La  Semaine  Medicale,  1897,  p.  114. 


BIBLIOGRAPHY. 


IT  has  seemed  to  me  best  to  give  a  list  only  of  the  books  and 
articles  which  I  have  found  most  useful,  since  the  general 
bibliography  of  the  subject  is  now  large  enough  to  form  a 
volume  by  itself.  Most  of  the  larger  works  here  described  con- 
tain extensive  bibliographies — especially  that  by  Grawitz. 

Text-Books. 

1.  Hayem:  "  Du  Sang,"  Paris,   1889,  8vo,  1035  pages  (French).     This 
valuable  book  is  the  largest  that  I  know  of  on  the  subject,  and  contains  a 
mine  of  information  on  the  morphology  of  the  blood  in  health  and  disease, 
mostly  from  the  author's  own  experience,  literature  being  but  little  re- 
ferred to.     It  contains  a  comparative  anatomy  of  the  blood  and  a  long 
account  of  blood  development.     Unfortunately,  it  is  dominated  through- 
out by  a  theory  of  blood  formation  which  has  never  gained  acceptance  by 
any  other  authority.     It  is  very  full  on  the  subject  of  fibrin  formation  and 
of  chlorosis.     The  illustrations  are  excellent. 

2.  v.    Limbeck  :  "  Grundriss  ein.   klin.   Pathologie  des  Blutes, "  Jena, 
1896,  8vo,  383  pages   (Fischer).     The  second  edition  of  this  book,  which 
appeared  in  February,  1896,  is  more  than  twice  the  size  of  the  first  edition 
(1892) — a  fact  illustrating  the  rapidity  of  the  subject's  growth.     It  is  on 
the  whole  the  best  general  text-book  known  to  me,  being  equally  full  on 
all  parts  of  the  subject,  including,  for  example,  technique  (which  Grawitz 
omits)  and  of  the  chemistry  of  the  blood,  which  is  at  present  the  author's 
special  interest  and  on  which  Hayem  is  meagre.     The  illustrations  are 
poor  and  the  type  is  trying  to  the  eyes.     The  writer  shows  little  personal 
experience  with  the  morphology  and  micro-chemistry  of  the  blood,  and 
this  is  the  weakest  side  of  the  book.     A  large  part  of  the  book  is  concerned 
with  the  physiology  of  the  blood. 

3.  Grawitz:   "Klinische  Pathologie  des  Blutes,"  Berlin,   1895,   8vo,  333 
pages  (Enslin).      Issued  in  April,  1896.     This  book  is  largely  devoted  to  the 
matter  indicated  by  the  title  and  contains  no  account  of  blood  technique,  and 
only  thirty  pages  on  the  normal  anatomy  and  physiology  of  the  blood,  while 
two  hundred  and  seventy  concern  the  blood  in  disease.     The  arrangement 
of  the  book  is  very  clear  and  helpful.     The  author's  main  interests  are  in 
the  estimation  of  the  dried  residue  of  the  blood  in  various  diseased  condi- 
tions and  in  the  bacteriology  of  the  blood,  so  that  the  book  is  specially  full 
on  these  topics.     The  illustrations  are  poor.     Type  and  paper  are  excellent. 

4.  Ehrlich  and  Lazarus:  "Die  Anaemie,"  Wien,   1898,  8vo,  142  pages 


430  BIBLIOGRAPHY. 

(Holder).  An  account  of  the  normal  and  pathological  histology  of  the 
blood  not  only  in  anaemia,  but  in  all  diseases  of  the  blood,  containing  the 
latest  researches  and  admirably  clear  as  regards  the  microscopic  appear- 
ances. This  is  Ehrlich's  latest  utterance — his  last  book  previous  to  this 
being  issued  in  1891  (vide  infra) .  It  contains  also  a  good  deal  of  inter- 
esting theoretical  discussion  OD  the  sources  and  formation  of  the  elements 
of  the  blood.  There  are  but  three  rather  indifferent  illustrations  (un- 
colored).  The  book  forms  part  of  vol.  iii.  in  Nothnagel's  new  "Special 
Pathology  and  Therapeutics, "  but  is  issued  separately. 

5.  Coles:  "The  Blood:    How  to  Examine  it,  "etc.,    London,    1898    (J. 
and  A.  Churchill) ,  8vo.     A  very  clear  account  of  our  present  knowledge 
on  the  subject.     Especially  full  on  technique. 

6.  Schmaltz:  "Pathologie  des  Blutes  und  die  Blutkrankheiten,"  Leip- 
zig, 1896,  16mo,  268  pages  (Naumann).     A  much  smaller  book  than  any  of 
the  others  and  including  the  symptoms,  pathology,  and  treatment  of  blood 
diseases,  as  well  as  a  pathology  of  the  blood  itself.     Specific  gravity  of  the 
blood  is  a  point  of  special  interest  with  the  author.     There  are  no  illustra- 
tions.    The  book  is  excellent  as  far  as  it  goes,  well  arranged,  and  clear. 

These  are  the  best  text-books  known  to  me  on  the  whole 
subject.     None  of  them  have  been  translated. 

Text-Book  Articles  on  Blood  Diseases. 

1.  Stengel's  article  in  vol.  vii.  of  the  "Twentieth  Century  Practice  of 
Medicine"  is  by  far  the  best  text-book  article  in  English  that  I  know  of. 

2.  Osier,  in  the  "  American  Text-book  of  the  Theory  and  Practice  of 
Medicine,"  vol.  ii.    (Philadelphia,   1894,   Saunders),   writes  an  excellent 
fifty -page  article  on  "  Diseases  of  the  Blood."     It  covers,  of  course,  only 
the  blood  diseases  proper  without  much  account  of  the  blood  in  other  con- 
ditions. 

3.  The  article  "The  Blood  in  Infancy, "  in  Rotch's  Paediatrics,  covers 
this  branch  of  the  subject  very  thoroughly. 

These  are  the  best  articles  in  English  that  I  know  of. 

4.  The  article  on  "  La  Pathologie  du  Sang, "  by  Gilbert,  in  the  five- 
volume  "  Traite  de  Medecine"  edited  by  Charcot,  Bouchard,  and  Brissaud, 
Paris,  1892  (Masson),  is  inferior  to  those  last  mentioned  and  is  mostly  an 
echo  of  Hay  em's  work  above  referred  to.     Theories  long  exploded  (e.g., 
that  eosinophiles  are  pathognomonic  of  leukaemia)  receive  the  author's 
sanction.     The  article  is  one  hundred  large  octavo  pages  long  and  is  in- 
tended to  cover  the  whole  subject. 

5.  Griffith's  eighty-page  article  in  Keating's  "  Cyclopaedia  of  the  Dis- 
eases of  Children,"  vol.  iii.,   p.  755  (Philadelphia,   1890,   Lippincott),    is 
now  a  good  deal  out  of  date. 

6.  The  articles  on  blood  diseases  in  the  latest  editions  of  the  text-books 
of  Osier,  Strumpell,  Da  Costa,  Flint,  and  Fagg,  contain  relatively  little 
about  the  blood  itself. 


BIBLIOGRAPHY.  431 


Treatises  on  Special  Portions  of  the  Subject. 

1.  Reinert's  "Die Zahlung  derBlutkorperchen,"  Leipzig,  1891  (Vogel), 
246  pages,    is  an  admirable  account  of   the  avoidable  and  unavoidable 
errors  in  blood  examination,  and  the  best  methods  of  reducing  error  to  a 
minimum.     A  number  of  careful  examinations  of  the  blood  in  health  and 
in  various  diseases  are  also  given  ;  and  an  outline  of  the  scope  of  blood 
diagnosis  closes  the  book. 

2.  v.    Noorden's  "Chlorosis"   (Wien,   1897,  8vo,    209  pages)    is  by   far 
the  best  piece  of  work  so  far  published  on  this  subject.     The  clinical  and 
therapeutic  sides  of  the  subject  are  fully  treated,  as  well  as  the  hsematolo- 
gical  pathology. 

3.  Turk's  monograph  on   the  "  Condition  of  the  Blood  in  A  cute  Infec- 
tious Disease"  is  an  admirable  resume  of  German  and  French  literature 
on  the  subject,  together  with  a  detailed  study  of  fifty-two  cases.     Published 
at  Wien  and  Leipzig,  1898  (Braumuller),  347  pages,  8vo. 

4.  Rieder's  "Beitrage  zur  Kenntniss  der  Leukocy tosis, "  Leipzig,  1892 
(Vogel),  220  pages,  is  an  admirable  work  in  all  respects,  although  now 
considerably  out  of  date.     It  shows,  as  very  few  of  the  foregoing  treatises 
do,  a  practical  acquaintance,    on  the  author's  part,    with  the  details  of 
blood  morphology  and  microchemistry.     A  very  large  number  of  blood 
counts  in  many  diseases  are  recorded. 

5.  Lowitt's    "Studien   zur   Physiol.    und    Pathol.    des  Blutes    u.    der 
Lymphe"  (Jena,  1892  [Fisher],  8vo,  138  pages)  is  mostly  concerned  with 
experiments  on  animals  and  intended  to  throw  light  on  the  theory  of  leu- 
cocytosis.     The  conclusions  of  the  book  have  not  been  generally  adopted, 
though  its  facts  have  been  mostly  verified. 

6.  Thayer  and  Hewetson's  book,  on  the  "Malarial  Fevers  of  Baltimore," 
leaves  nothing  more  to  be  desired  in  that  direction.     It  is  two  hundred 
and  fifteen  pages  long,  published  by  the  Johns  Hopkins  press  of  Baltimore 
in  1895.     It  contains  a  summary  of  the  literature  of  the  subject,  an  analy- 
sis of  six  hundred  and  sixteen  new  cases,   and  some  admirable  colored 
plates.     It  is  a  model  of  its  kind  in  every  respect,  and  an  ideal  for  others 
to  aim  for. 

7.  Ehrlich's  "  Farbenanalytische  Untersuchungen"  (Berlin,  1891  [Hirsch- 
wald],  137  pages)  contains  nine  short  essays  by  Ehrlich  and  three  by  his 
pupils.     Considering  the  reputation  of  the  writer  they  are  at  the  present 
day  rather  disappointing  reading,  and  contain  little  that  is  not  better 
expressed  elsewhere. 

8.  Weiss's    "  Haematologische  Untersuchungen"    (Wien,    1896    [Proc- 
kaska]  112  pages,  8vo)  contains  many  valuable  studies  on  various  points. 

9.  Under  a  somewhat  different  heading  come  the  sections  on  the  ex- 
amination of  the  blood    in  v.   Jaksch's   "Clinical   Diagnosis"    (English 
translation,    London,    1893,   Griffen   &   Co.),    a  seventy-five-page  article 
containing  many  inaccuracies;  and  Lenharz :  "Microscopic  und  Chemie 
am  Krankenbett"  (Berlin,  1896,  Springer) ,  a  fifty-page  article. 


432  BIBLIOGRAPHY. 


Magazine  Articles  of  Special  Value. 

1.  On  Concentration  and  Dilution  of  the  Blood — Oliver  :  Lancet,  June 

27,  1896. 

2.  On  Leucocytosis — Goldschneider  and  Jacob:  Zeit.  fur  klin.  Med., 
1894,  vol.  25.     Krebs :  Inaug.    Dissert. ,    Berlin,    1893.      Sadler :  Forschr. 
d.  Med.,  Supplement-Heft,  1892.     Also  Klein,  in  Volkmann's  Sammlung 
klinischer  Vortrage,  December,  1893,  and  of  course  Rieder  and  Turk  above 
referred  to. 

3.  On  Anaemia — Dunin  :  Volkmann's  Sammlung.  klin.  Vortrage,  1896, 
No.  135.     Romberg :  Berlin,  klin.  Woch. ,  June  28,  1897. 

4.  Parasitic  Anaemia — Schaumann  :  Zur  Kenntniss  der  sog.  Bothrio- 
cephalus  Anamie,   Berlin,   1892,   214  pages ;   and  Askanazy  :  Zeitschr.   f. 
klin.    Med. ,    1895,   p.   492.     Brown  :  Journal  of  Experimental   Medicine, 
May,  1898  (Trichinosis). 

5.  Leukaemia — Fraenkel :  Deutsche  med.  Wochenschrift,   1895,  p.  639. 
Fraenkel:   15th  Congress  fiir  inn.   Medicin.   Wiesbaden,   1897.      Benda : 
Ibidem.     Dock  :  Moscow  Internat.  Congress,  1897. 

6.  Pernicious    Anaemia — Discussion     by    Birch-Hirschfeld,    Ehrlich, 
Troje,  and  others,  at  the  XI.  Congress  f .  inner.  Med.   (Leipzig,  1892) . 

7.  Pneumonia — Billings  :  Bulletin  of  the  Johns  Hopkins  Hospital,  No- 
vember,  1894.     Diphtheria — Billings :   New  York  Medical  Record,  April 
25,   1896.     Typhoid— Thayer :  Johns   Hopkins  Hospital  Reports,   vol.    iv., 
No.  1.     Engel:  15th  Congress  fur  inn.  Med.,  Wiesbaden,  1897.     Exanthe- 
mata—Felsenthal  :  Arch,  f .  Kinderheilk. ,  1892,  p.  78.     Zappert :  Zeitschr. 
f .  klin.   Med. ,   1893,  No.  23.     Small-pox— Pick  •  Arch,  f .   Dermatol.  und 
Syph.,    1893,    p.    63.      Sepsis— Roscher :    Inaug.    Dissert,    Berlin,    1894. 
Cholera— Biernacki :  Deutsche  med.  Wochenschr.,  1895,  No.  48.     Diabetes 
— Bremer  :  Moscow  Internat.  Congress,  1897. 

8.  Syphilis— (a)  Reiss  :  Arch.  f.  Dermat.  und  Syph.,  1895,  Hf.  1  and  2. 
(6)  Justus:  Virchow's  Arch.,  1895. 

9.  Tuberculosis — (a)  Dane  :  Boston  Medical  and  Surgical  Journal,  May 

28,  1896.      (6)  Stein  und  Erbmann  :  Deutsche  med.  Wochenschrift,   1896, 
No.  56,  p.  323.     (c)  Grawitz :  Deutsche  med.  Wochenschr.,  1893,  No.  51. 

10.  Malignant  Disease — Taylor  (International  Medical  Magazine,  July, 
1897).     (a)  Sadler:  Loc.  cit.     (b)  Reinbach  :  Langenbeck's  Archiv,  1893, 
No.  46.     (c)  Strauer:  Dissert.,  Greifswald,  1893. 

11.  Bacteriology — Sittmann  :  Deutsches  Arch.  f.  klin.  Med.,  vol.  53. 

12.  Diseases  of  the  Stomach  (especially  Cancer)  — Schneyer  :  Zeitschrif t 
f.  klin.  Med.,  1895,  p.  475.    Osterspey :  Inaug.  Diss.,  Berlin,  1892. 

13.  Eosinophiles— Zappert:  Zeitschr.  f.  klin.  Med.,  1893,  vol.  23. 

14.  Haemoconien— Miiller :  Wien.  med.  Presse,  1896,  No.  36. 


INDEX. 


ABSCESS,  223 

iodine  reaction  in,  223 
of  liver,  196,  292 
of  lung,  236 
other  forms  of,  234 
pericsecal,  223 
perinephritic,  234 
subphrenic,  235 
Acetic  acid,   solution  for  counting 

white  corpuscles,  18 
Actinomycosis,  108,  239 
Acute  anaemia,  190 
Acute  delirium,  315 

yellow  atrophy  of  the  liver,  289 
Addison's  disease,  126,  320 

myelocytes  in,  121 
Adenitis,  175 

tubercular,  267 
Alkalinity,  48 

in  cholera,  212 
in  diabetes,  316 
in  fever,  183 
in  gout,  317 
in  osteomalacia,  321 
in  rheumatism,  207 
Altitude,   effect  on  blood,  79 
Amyloid  disease,  175 
Anaemia,  82 

causes  of,  94 

classification  of,  in  infancy,  388 
color  of  skin  and  mucous  mem- 
branes in,  82 

destruction  of  corpuscles  in,  89 
due  to  intestinal  parasites,  383 
in  infancy,  387 

infautum  pseudoleukaemica,391 
in  gastric  atrophy,  275 
leucooytosis  in,  388 
myelooytes  in,  121 
nucleated  red  cells  in,  89 
pernicious,    133-151 
post-febrile,   191 
primary  and  secondary,  84 
red  corpuscles  in,  85 
stages  in  secondary,  85 
splenic  hyperplasia  in,  387 
white  cells  in  (see  Leucocytosis) 
Aneurism,  299 
Ankylostoma  duodenale,  383 
28 


Antipyretics,  effect  on  leucocytes, 
186 

effect  on  red  cells,  183,  327 
Antipyrin,  eosinophilia  from,  118 

leucocytosis  from,  110 
Aoyoma,  238 
Appendicitis,  223 
Arthritisj  gonorrhoeal,  210 

septic,  210 
Asiatic  cholera,  211 
Asthma,  bronchial,  309 

cardio-renal,  310 

BACTERIA  in  blood,  383 

in  blood  of  sepsis,  215 
Bacteriological  examination  of  the 

blood,  47 

Barlow's  disease,  325 
Basedow's  disease,  320.  (See  Graves' 
Disease. ) 

eosinophilia  in,  116 

lymphocytosis  in,  116 

myelocytes  in,  121 
Basophilic  cells,  66,  168 

granules,  Neusser'sperinuclear, 

399 

Beri-beri,  241 

Blood,  bacteriological  examination 
of,  47,  383 

counting,  11 

crises,  128 

destruction,  324 

examination     of      dried     and 
stained,  61 

examination  of  fresh,  5 

examination,  value  of,  3 

in  infancy,  385 

normal  appearances  of,  9,  50,  61 

plates,  53,  59 

"Blood-Dust"  (Miiller's),  59 
Bone  diseases,  eosinophilia  in,  116 

tuberculosis,  259,  120 
Bothriocephalus  latus,  383 
Brain  diseases,  312 
Bronchitis,  189,  194,  307 

acute,  307 

chronic,  308 

Brownian  motion,  9,  363 
Bubonic  plague,  425 


434 


INDEX. 


Burns,  haemoglobinaemia  in,  327 
myelocytes  in,  120 

CACHEXIA,  cancerous,   red  cells  in, 

88,  332 
Cancer,  332 

anaemia  in,  333 

effect  of  metastases  in,  344 

lack  of  anaemia  in,  334 

leucocytes  in,  338 

effect  of  position  of,  339 

of  breast,  340 

of  gullet,  345 

of  intestine,  347 

of  kidney,  348 

of  liver,  346 

of  omen  turn,  348 

of  stomach,  341 

of  uterus,  349 

percentage  of  haemoglobin  in, 

334 
Carbonic  acid  poisoning,   80,   121, 

327 

Carcinoma  (see  Cancer). 
Castration,  effects  of,  116-118 
Cell  death,  prevention  of,  8 
Cerebral  disease  (see  Brain). 
Cerebral  hemorrhage,  128,  251 

tumors,  251,  313 

Cerebro-spinal  meningitis  (epidem- 
ic), 249 

Charcot-Leyden  crystals,  169 
Chicken-pox,  207 

Childbirth,  influence  on  red  cells, 
56 

influence  on  white  cells,  102 
Chloroform-benzol,   use  of,  in  esti- 
mating specific  gravity,  40 
Chlorosis,  152 

haemoglobin  in,  152 

infantile,  389 

myelocytes  in,  121 

red  cells  in,  153 

specific  gravity  in,  156 

white  cells  in,  156,  158 

without  known  blood  changes, 

159 

Cholaemia,  290 
Cholangitis,  285,  291 
Cholera,  Asiatic,  211 
Chorea,  313 
Cirrhotic  liver,  286 

changes  in  red  cells  in,  78,  89 

hyper  trophic  forms  of,  288 
Coagulation,  49,  324 
Cold,  effects  of,  58,  102 
Colic,    hepatic  and  renal,  229,  290, 
305 

intestinal,  229 
Colitis,  282 


Color  index,  123 

Color  of  blood  in  chlorosis,  152 

of  blood  in  leukaemia,  160 

of  blood  in  pernicious  anaemia, 
133 

of  skin  in  anaemia,  82 
Coma,  blood  in,  251 
Concentration  of  blood,  57,  76,  296 
Convulsions,  leucocvtes  in,  314 
Cornil's  "  Mark  cells,""  71 
Counting,  difficulties  of,  15 

of  red  cells,  11-18 

of  white  cells,  18-22 
Cover-glasses,  cleaning  of,  7,  43 

method  of  holding,  7 

necessity  of  cleanliness,  7 

preparations,  43 
Crenation,  50,  86 
Cretinism,  319 

Cyanosis,   general,  effect  on  blood, 
74,  296 

local,  74 

Cysticercosis,  312 
Cystitis,  leucocytes  in,  108,  194 

myelocytes  in,  121 

DEBILITY,  effect  on  red  cells,  315 

effect  on  white  cells,  67,  68,  114 
Degenerative  changes  in  red  cells, 

53,  84 

Dermatitis,  109 
Diabetes,  myelocytes  in,  121 
Diabetic  coma,  316 
Diarrhoea,      concentration     of    the 

blood  in,  76 
chronic,  282 

Differential  counting,  method  of,  46 
Digestion  leucocytosis,  99 

leucocytosis  in  gastric  cancer, 

343 
leucocytosis  in  gastric  catarrh, 

279 

leucocytosis  in  gastric  ulcer,  276 
Dilatation  of  the  stomach,  280 
Dilution  of  the  blood,  12,  57,  78 
Diphtheria,  197 

effects  of  antitoxin,  198 
leucocytosis  in,  199 
lymphocytosis  in,  200 
myelocytes  in,  200 
red  corpuscles  in,  197 
Distomum  haematobium,  382 
Dried  preparations  cf  blood,  43 

preparations  of  blood,  red  cells 

in,  61 
preparations    of    blood,    white 

cells  in,  62 
residue  of  blood,  estimation  of, 

275 
Duodenal  ulcer,  277,  327 


INDEX. 


435 


Durham's  blood  counter,  22 
Dysentery,  282 
Dyspepsia,  278 

EAR,  puncturing  the,  6 
Eczema,  109 

Effusions,  serous,  76,  242 
Emphysema,  309 
Empyema,  244 
Endocarditis,  293 

ulcerative,  215,  293 
Endoglobular  changes  in  red  cells, 

86 
Enteritis,  acute,  279,  282 

chronic,  282 

Eosinophiles,    appearance  in  fresh 
blood,  52 

appearance  in  stained  blood,  65 

in  malignant  disease,  350,  356 

in  normal  blood,  67 

life  history  of,  68 
Eosinophilia,  116-119,  156,  204,  239, 

309,  350,  356 

Eosinophilic  myelocytes,  71,  167 
Epidemic  dropsy,  240 
Epilepsy,  coma  after,  251 

red  cells  in,  89 

white  cells  in,  119,  314 
Erysipelas,  89,  212 
Etat  cribriforme,  286 
Exercise,  effect  on  blood,  56 


impaction,  230 
Fatigue,  effects  on  blood,  57 
Felon,  108,  234 

Fever,  influence  on  the  blood,  183 
Fibrin  network,  53,  54 

network,  general  pathology  of, 

124 

network,  in  cancer,  332 
Filaria  sanguinis  hominis,  374 

sanguinis     hominis,    examina- 

tion for,  375 
Fixation  of  blood  films  by  alcohol 

and  ether,  43 

of  blood  films  by  heat,  43,  44 
Fleischl's  haemometer,  33-37 
Floating  kidney,  229,  307 
Furunculosis,  108 

GALL-STONES,  290 

Gas,  illuminating:,  poisoning:  by,  80, 

109,  121,  327 
Gastric  cancer,  341 

dilatation,  280 

ulcer,  275 
Gastritis,  278 

chronic,  279 

corrosive,  281 
Gastro-  enteritis,  276-278 


General  paralysis  of  the  insane,  121, 
312 

Genitals,  influence  on  blood.  116, 
117 

Glanders,  238 

Glands  (see  Adenitis) 

Gonorrhoea,  117,  236 

Gout,  317 

Gowers'  solution,  12 

Graves'  disease,  320 

Gravity,  specific,  method  of  esti- 
mating, 40,  125 

Grippe,  113,  214 

HJEMATOCRIT,  accuracy  of,  30 
advantages  of,  30 
method  of  using,  30-33 

Haematology,  3 

Haemocytolysis,  326 

Haemoglobin,  estimation  of,  33-40 
general  pathology  of,  123 
in  chlorosis,  152 
indirect   estimation  of,  by  spe- 
cific gravity,  41 
in  malignant  disease,  334,  353 
in  pernicious  anaemia,  134 

Hsemoglobinaemia,  89,  218,  326 
paroxysmal,  326 

Haemoglobinometer,  Fleischl's,  33 
Oliver's,  38 

Haemophilia,  6,  325 

Hemorrhage,  106,  126    ' 

hemorrhage,  cerebral,  312 

Hemorrhagic  diseases,  324 

Heart,  diseases  of,  293 

diseases,  of,  aortic,  298 
diseases    of,    concentration    of 

blood  in,  296 

diseases  of,  congenital,  298 
diseases  of,    dilution  of  blood 

in,  297 

diseases  of,  leucocytes  in,  297 
diseases  of,  mitral,  298 

Herpes  zoster,  109 

Hodgkin's  disease,  177 

disease  in  infancy,  395 
disease,  myelocytes  in,  181 
disease,  transition  to  leukaemia, 

177 
disease,  white  cells  in,  181 

Hydatid,  235,  289 

Hydraemia,  82,  95 

Hydronephrosis,  175 

Hyperacidity  and  hypersecretion, 
280 

Hypochondriasis,  314 

Hysteria,  117,  251,  314 

ICTERUS  of  the  new-born,  285 
Illuminating  gas,  poisoning  by,  330 


436 


INDEX. 


Infancy,  anaemias  of,  387 

blood  in,  385 

eosinophilia  in,  116,  117 

haemoglobin  in,  386 

leukaemia  in,  397 

lymphocytosis  in,  114 
Influenza,  214 
Insanity,  anaemia  in,  315 

eosinophilia  in  acute,  119,  315 
Intestine,  cancer  of,  348 

diseases  of,  281 

obstruction  of,  284 
Isotonia,  isotonic  coefficient,  49 

JAUNDICE,  catarrhal,  changes  of  red 

cells  in,  89 
catarrhal,    increased  resistance 

of  red  cells  in,  284 
catarrhal,   volume  of  red  cells 

in,  284 
in  pneumonia,  185 

KIDNEY,  cancer  of,  348 
diseases  of,  299 
diseases  of,  acute,  300 
diseases  of,  chronic,  301 
floating,  229,  307 
floating,  cyst  of,  175 
stone  in  the,  305 

LACTATION,  influence  on  red  cells,  56 
Lactic  acid,    in  blood  of  rheuma- 
tism, 207 
Lead  encephalopathy,  251 

poisoning,  changes  of  red  cells 

in,  89 

Leprosy,  272 
Leucocytosis,  96 

absence  of,  113 

after  cold  baths,  exercise,  mas- 
sage, 102 

after  parturition,  102 

atypical  leucocytes  in,  112 

definition  of,  96 

diagnostic  value  of,  100 

from  therapeutic  influences,  110 

inflammatory,  106-109 

in  infancy,  101,  388 

of  digestion,  99,  276,  279,  343 

of  malignant  disease,  338,  354 

of  pregnancy,  101 

of  the  moribund,  105 

of  the  new-born,  101,  385 

pathological,  106-114 

physiological,  98 

post-hemorrhagic,  106 

toxic,  109 
Leucopenia,  113 

in  anaemia,  113 

in  infectious  diseases,  IIP 


Leucopenia  in  starvation,  113 
Leukaemia,  160-176,  397 
adult  leucocytes  in,  166 
anaemia  in,  162 

Charcot-Leyden  crystals  in,  169 
effects  of  intercurrent  infections 

in,  176 

eosinophiles  in,  116,  167 
haemoglobin  in,  161 
in  infancy,  394 
lymphatic,  169 
lymphocytes  in,  168-170 
megaloblasts  in,  162-170 
myelocytes  in,  165 
Neusser's  granules  in,  169 
ndrmoblasts  in,  162,  170 
red  corpuscles  in,  89,  161,  170 
septicaemia  in,  171 
splenic-myelogencus,  160-167 
white  cells  in,  162,  170 
Lipsemia,  125,  315-316 
Liver,  abscess  of,  292 

acute  yellow  atrophy  of,  109,  289 
cancer,  346 
cirrhosis,  286 
cholangitis,  286,  291 
diseases  of  the,  284 
gumma,   293 
hydatid  of,  289 
Lungs,  diseases  of,  307 
Lymphaemia,  169 
Lymphocytes,  appearances  of,  62 
percentage  among  white  cells, 

67 
Lymphocytosis,  114 

in  chlorosis,  114,  157 

in  Graves'  disease,  114,  121,  320 

in  infancy,  114,  385 

in  leukaemia,  167-169 

in  malignant  disease,  349,  356 

in  pernicious  araemia,  114,  145 

in  pneumonia,  115,  188 

in  rickets,  322 

in  syphilis,   114,  270,  385 

in  thyroid  feeding,  115 

in  typhoid  fever,  195 

MALARIA,  361 

absence  of  leucocytes  is  in,  113 
blood  destruction  in,  89 
haemoglobinaemia  in,  374 
haemoglobin  in,  372 
myelocytes  in,  122 
parasite  of,  362 

parasite  of,  crescentte  forme,  367 
parasite  of,  flagellate  forms,  367 
parasite  of,  hyaline  forms,  362 
parasite  of,pigmented  forms,  363 
parasite  of,  segmenting  forms, 
366 


INDEX. 


437 


Malaria,  preparation  of  stained  spec- 
imens, 370 

red  cells  in,  89,  372 

white  cells  in,  373 
Malignant  disease  (see  Cancer  and 
Sarcoma),  332 

disease,    differential    diagnosis 
of,  359 

disease,     summary     of     blood- 
changes  in,  358 
Malta  fever,  238 
Marrow,  eosinophiles  in,  67 

rnyelocytes  in,  67 
Measles,  205 

leucocytes  in,  113,  205 

red  cells  in,  89,  205 
Measuring  corpuscles,  55 
Megaloblasts,  91 

in  chlorosis,  155 

in  malignant  disease,  339        , 

in  parasitic  anaemia,  384 

in  pernicious  anaemia,  141 

in  secondary  ansemia,  94 
Melanaemia,  126,  320 
Meningitis,  248 

cerebro-spinal,  249,  251 

tubercular,  265 
Menstruation,  effect  on  red  cells,  56 

eosinophiles  in,  116 
Microblasts,  94 
Mitosis,  68 
Molecular  motion  in  corpuscles,  9, 

50,  363 

Mononuclear  neutrophiles,  65,  72 
Movable  stage,  use  of,  in  differential 

counting,  46 
Mumps,  205 
Myelocytaemia,  161 
Myelocytes,  69,  72,  120 

in  cancer,  351 

in  leukaemia,  165 

in  other  conditions,  121 

in  pernicious  anaemia,  146 

in  sarcoma,  357 
Myocarditis,  295 
Myxoeiema  and  cretinism,  276 

NECROBIOSIS  of  red  cells,  85 
Nephritis,   300 

acute,  300 

chronic,  302 

chronic  diffuse,  301 

chronic  interstitial,  304 

parenchymatous,  301 

necrobiotic  changes  in,  87 

red  cells  in,  88,  300 
Nervous  system,  diseases  of,  311 
Neuralgia,  312 
Neuritis,  alcoholic,  311 


Neuritis,  acute  multiple,  311 
Neusser's  granules,  258,  377 
Neutrophilic  granules,  64,  69 
Newton's  rings,  14 
Normoblasts,  90,  94 
in  chlorosis,  155 
in  infantile  blood,  386 
in  pernicious  anaemia,  141 
in  secondary  anaemia,  94 
Nuclein,  eosinophilia  from,  119 

leucocytosis  from,  110 
Nucleated  red  corpuscles,  89 

red   corpuscles,   atypical  forms 

of,  92 

red  corpuscles  in  anaemia  of  in- 
fants,  391 

red  corpuscles  in  chlorosis,  155 
red  corpuscles  in  malignant  dis- 
ease, 338 

red  corpuscles  in  pernicious  an- 
aemia, 144 
red  corpuscles  in  tuberculosis, 

254 
Nutrition,  effects  on  blood,  57 

OBESITY,  315 

Obstruction,  intestinal,  284 
Omentum,  cancer  of,  348 
Operations,   surgical,  contraindica- 
tions in  the  blood,  130 

surgical,  effect  on  leucocytes  in 
cancer,  341 

surgical,  loss  of  blood  in,  127 
Osteomalacia,  321 

eosinophiles  in,  116 

myelocytes,  in,  120 
Osteomyelitis,  117,  121,  234 

tubercular,  259 
Osteosarcoma,  355 
Otitis  media,  194,  233 
Oval  corpuscles,  87 

PACHYMENINGITIS  HJEMORRHAGICA, 

313 
Parasites  of  the  blood,  361 

intestinal,      influence     on     the 
blood,  383 

malarial  'see  Malaria) 
Paresis,  313 

Pellagra,  eosinophilia  in,  116 
Pelvic  abscess,  231 

neuralgia,  229 

Pemphigus,  eosinophilia  in,  116  • 
Pericarditis,  serous,  247 

tubercular,  267 

Perinuclear  basophilia,  258,  399 
Peritonitis,  228,  245 

general  septic,  245 

granular,  246 

pelvic,  231 


438 


INDEX. 


Peritonitis,  tubercular,  264 
Pernicious  anaemia,  133 

anaemia,    changes  of  red  cells 
in,  89,  134,  140 

anaemia,  diagnosis  of,  147 

anaemia,  eosmophiles  in,  146 

anaemia,  haemoglobin  in,  138 

anaemia  in  infancy,  395 

anaemia,  lymphocytes  in,  145 

anaemia,  megaloblast.s  in,  144 

anaemia,  myelocytes  in,  146 

anaemia,     necrobiotic    changes 
in,  88 

anaemia,  relapse  in,  134,  136 

anaemia,  white  cells  in,  136 
Perspiration,  effect  on  blood,  57 
Phenacetin  poisoning,  327 
Phlebitis,  194 

Phosphorus  poisoning,  80,  119,  290 
Phthisis,  253 

anaemia  of,  253 

eosinophiles  in,  119,  258 

fibroid,  25 

myelocytes  in,  120,  258 

white  corpuscles  in,  255 
Physiology  of  blood,  50-71 
Pipette  (see  Thoma-Zeiss)  cleaning 

of,  18 

Pilocarpine,  leuc  cytosis  after,  110 
Plague,  bubonic,  238 
Plethora,  73-80 

possibility  of  a  true,  80 
Pleurisy,  242 

purulent,  244 

serous,  242 

tubercular,  243,  267 
Pneumonia,  184 

artificial   production  of  leuco- 
cytosis  in,  185 

bacteriology  of  blood  in,  184 

coagulation  in,  184 

leucocytes  in,  185 

prognosis  in,  185 

red  cells  in,  185 
Poikilocytosis,  86 
Poisoning,  alcoholic,  331 

corrosive,  330 

opium,  330 

ptomain,  331 
Polychromatophilic      changes      in 

pernicious  anaemia,  141 
Polycythaemia,  73-75,  79 
Polymorphonuclear  cells,  64-67,  166 
Polymorphous  blood   in  leukaemia, 

169 
Potassium,   chlorate   of,    poisoning 

by,  327 
Pregnancy,  56 

extra-uterine,  230 


Puerperal  m&viia,  315 

mania,  myelocytes  in,  120 

sepsis,  218 

Puncture  of  the  ear  in   blood   ex- 
amination, 5 
Purgation,     concentration     of    the 

blood  in,  76,  281 
Purpura,  324 

changes  of  red  cells  in,  88 

necrobiotic  changes  in,  88 
Pus  tube,  231 
Pyaemia,  216 

changes  of  red  cells  in,  88 
Pyelo-nephritis,  305 
Pyonephrcsis,  307 

QUININE,  effect  on  blood  in  fever,  183 
poisoning,  leucocytes  of,  109 

RATIO  of  red  to  white  cells,  estima- 
tion in  fresh  blood,  9 
of  red  to  white  cells,  estimation 

in  stained  specimei  s,  61 
Regeneration  of  blood  after  hemor- 
rhage, 127 
of    blood    after    operation    for 

cancer,  335 
Relapsing  fever,  425 
Resistance  of  blood  to  water,  elec- 
tricity, etc.,  48 

Rheumatism,  acute  articular,  207 
chronic  articular,  210 
muscular,  210 
red  cells  in,  208 
subacute,  210 
white  cells  in,  209 
Rickets,  322 

anaemia  in,  322,  389 
leucocytosis  in,  323 
lymphocytosis  in,  114,  323 
myelocytes  in,  122,  323 
Rotheln,  113,  205 
Rouleaux  formation,  50 

SALINE  cathartics,  influence  of,  on 

the  blood,  281 
solution,  normal,  128 

Sarcoma,  353 

anaemia  in,  353 
eosinophilia  in,  116,  356 
leucocytes  in,  354 
myelocytts  ir,  120,  356 

Scarlet  fever,  203 

changes  of  red  cells  in,  89 
eosinophilia  in,  204 
leucocytosis  in,  203 
necrobiotic  changes  in,  89 

Scurvy,  324 


INDEX. 


439 


Scurvy,  lymphocytes  is  in,  114 
Secondary  anaemia,  82-95 

causes  of,  95 

grades  of,  94 

Maragliano's  degenerative 
changes  in,  89 

nucleated  red  corpuscles  in,  90 
Sepsis,  215 

bacteria  in  blood  of,  215 

in  leukaemia,  171 

in  wounds,  215 

leucocytes  in,  216 

myelocytes  in,  120 

puerperal,  218 

red  cells  in,  216 

streptococcus,  218 
Sero-diagnosis,  400 

in  bubonic  plague,  425 

in  cholera,  422 

in  colon-bacillus  infections,  423 

in  diphtheria,  422 

in  hog  cholera,  424 

in  Malta  fever,  424 

in  peripneumonia  of  cattle,  424 

in  pneumococcus  infections,  422 

in  proteus  infections,  424 

in  psittacosis,  424 

in  pyocyaneus  infections,  423 

in  relapsing  fever,  425 

in  scarlet  fever,  426 

in  septicaemia,  426 

in  tetanus,  426 

in  thrush,  425 

in  typhoid,  415 

in  yellow  fever,  425 
Sero-prognosis,  427 
Serum,  examination  of,  408 

clump  reaction,  general  descrip- 
tion, 401 

clump-reaction  technique,  402 

dried  blood,  use  of,  405 

cultures,  how  prepared,  409 

dilution  and  the  time  limit,  412 

fluid  blood,  use  of,  404 

fluid  serum,  use  of,  407 
Skin  diseases,  eosinophilia  in,  116, 

117 
Small-pox,  206 

leucocytes  in,  206 

pneumonia  in,  185 

red  cells  in,  89,  206 
Solids,  estimation  of,  in  blood,  49 
Spinal  cord,  chronic  diseases  of,  313 
Spirochaete  of  relapsing  fever,  379 
Spleen,    hypertrophy  of,   in  rickets 
and  all  anaemias  of  infancy, 
385 

tumors  of,  119 
Splsnectomy,  effects  on  blood,  183 


Staining,  Biondi-Heidenhain  form- 
ula, 44 

Ehrlich-Biondi  formula,  44 
fluid,  Ehrlich's  latest,  44 
mast-cells,  66 
Neusser's  perinuclear  basophilic 

granules,  Appendix, 
of  red  cells  when  degenerated,  89 
the  malarial  parasite,  370 
Starvation,  effects  of,  on  blood,  57, 76 
Stomach,  274 

cancer  of,  341 

channels  of,  influence  on  blood, 

274 

dilatation  of,  280 
inflammation  of,  278 
ulcer  of,  275 
Suprarenal    extract,    concentration 

of  blood  by,  77 

Surgery,    value  of  blood  examina- 
tions in,  129,  221,  223,  335 
Sweating,    concentration    of   blood 

in,  76 
Sympathetic    nervous    system,    in- 

'fluenceon  blood  of,  116,  118 
Syphilis,  268 
of  lung,  310 

anaemia  in,  268  and  389  seq. 
cerebral,  313 

changes  of  red  cells  in,  89 
effects  of  mercury  on  the  blood 

in,  269 

eosinophilia  in,  118,  271 
haemoglobin  in,  270 
leucocytosis  in,  270 
lymphocytosis  in,  114 
myelocytes  in,  120,  271 

TETANUS,  241 
Tetauy,  313 

Thoma-Zeiss  blood  counter,  accuracy 
of,  15,  26 

blood  counter,  cleaning  of,  17 

blood   counter,    disadvantages, 
26 

blood  counter,  use  of,  11-21 

counting  slide,  15 
Tintometer  (Oliver's),  26 
Toisson's  solution,  12 
Tonsillitis,  213 
Toxic  leucocytosis,  109 
Transitional  leucocytes,  63 
Trichinosis,  239 

eosiuophilia  in,  119 
Tropical  anaemia,  82 
Tubercular  pneumonia,  256 
Tuberculin,  119,  256 
Tuberculosis,  253 

acute  miliary,  26i 


440 


INDEX. 


Tuberculosis,   changes  in   red  cells 
in,  89,  253,  390 

genito-urinary,  268 

leucopenia  in,  262 

leucocytes  in,  114,  255-264 

of  bones,  259 

of  serous  membranes,  264 

pulmonary,  255 

Tumors  (see  Cancer  and  Sarcoma) . 
Typhoid,  191 

anaemia  in,  191 

bacteriology,  191 

changes  of  red  cells  in,  89 

diagnosis  of,  191 

effects  of  complications,  194 

effects  of  intestinal  perforation 
in,  194 

leucocyte-sis  in,  193 

leucopenia  in,  113,  193 

serum-diagnosis  in,  415 
Typhus,  237 

necrobiotic  changes  in,  89 

UR/EMIA,  303 
Uric-acid  diathesis,  317 
Urine,    examination  of,   compared 
with  blood  examination,  3 


Uterus,  cancer  of,  349 

VARIOLA,  180 
Varicella,  180 
Vasomotor  influences,  effect  on 

blood,  57,  74 
Volume   of  red  cells  estimated  by 

hsematocrit,  26 
Vomiting,    concentration    of  blood 

in,  76 

WARM-STAGE,  use  of,  9 

White    corpuscles,    amoeboid    and 

non- amoeboid  forms,  52 
corpuscles,    description    of,     in 

fresh  blood,  52 
corpuscles,  distinguishing  them 

from  red,  18 
corpuscles,  normal  number  of, 

59 

Whooping-cough,  206 
Wounds,  septic,  219 

XANTHIN  bases,  effect  c.',  in  blood, 
120,  259 

YELLOW  fever,  236,  425 


RETURN  TO  DESK  FROM  WHICH  BORROWED ! 


IB<                        1 

This  book  is  due  on  the  last  date  stamped  below,  or 
on  the  date  to  which  renewed. 
Renewed  books  are  subject  to  immediate  recall. 

-~~^tlSSSS~ 

p> 

JflWfc  '58 

frT'tTFi 

MAR  15  13/3 

MAR  1  5  1973  /7 

